TY  - JOUR
AB  - High-linear energy transfer (LET) radiation, such as heavy ions is associated with a higher relative biological effectiveness (RBE) than low-LET radiation, such as photons. Irradiation with low- and high-LET particles differ in the interaction with the cellular matter and therefore in the spatial dose distribution. When a single high-LET particle interacts with matter, it results in doses of up to thousands of gray (Gy) locally concentrated around the ion trajectory, whereas the mean dose averaged over the target, such as a cell nucleus is only in the range of a Gy. DNA damage therefore accumulates in this small volume. In contrast, up to hundreds of low-LET particle hits are required to achieve the same mean dose, resulting in a quasi-homogeneous damage distribution throughout the cell nucleus. In this study, we investigated the dependence of RBE from different spatial dose depositions using different focused beam spot sizes of proton radiation with respect to the induction of chromosome aberrations and clonogenic cell survival. Human-hamster hybrid (AL) as well as Chinese hamster ovary cells (CHO-K1) were irradiated with focused low LET protons of 20 MeV (LET = 2.6 keV/µm) beam energy with a mean dose of 1.7 Gy in a quadratic matrix pattern with point spacing of 5.4 × 5.4 µm2 and 117 protons per matrix point at the ion microbeam SNAKE using different beam spot sizes between 0.8 µm and 2.8 µm (full width at half maximum). The dose-response curves of X-ray reference radiation were used to determine the RBE after a 1.7 Gy dose of radiation. The RBE for the induction of dicentric chromosomes and cell inactivation was increased after irradiation with the smallest beam spot diameter (0.8 µm for chromosome aberration experiments and 1.0 µm for cell survival experiments) compared to homogeneous proton radiation but was still below the RBE of a corresponding high LET single ion hit. By increasing the spot size to 1.6-1.8 µm, the RBE decreased but was still higher than for homogeneously distributed protons. By further increasing the spot size to 2.7-2.8 µm, the RBE was no longer different from the homogeneous radiation. Our experiments demonstrate that varying spot size of low-LET radiation gradually modifies the RBE. This underlines that a substantial fraction of enhanced RBE originates from inhomogeneous energy concentrations on the µm scale (mean intertrack distances of low-LET particles below 0.1 µm) and quantifies the link between such energy concentration and RBE. The missing fraction of RBE enhancement when comparing with high-LET ions is attributed to the high inner track energy deposition on the nanometer scale. The results are compared with model results of PARTRAC and LEM for chromosomal aberration and cell survival, respectively, which suggest mechanistic interpretations of the observed radiation effects.
AU  - Ilicic, K.
AU  - Dollinger, G.*
AU  - Dombrowsky, A.
AU  - Greubel, C.*
AU  - Girst, S.*
AU  - Sammer, M.*
AU  - Siebenwirth, C.*
AU  - Schmid, E.*
AU  - Friedrich, T.*
AU  - Kundrát, P.*
AU  - Friedland, W.
AU  - Scholz, M.*
AU  - Combs, S.E.
AU  - Schmid, T.E.
AU  - Reindl, J.*
C1  - 69756
C2  - 55256
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 140-149
TI  - Enhanced RBE of particle radiation depends on beam size in the micrometer range.
JO  - Radiat. Res.
VL  - 201
IS  - 2
PB  - Radiation Research Soc
PY  - 2024
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - In this study, the preparation and characterization of copper (Cu) and terbium (Tb) co-doped lithium borate glass using spectroscopic and thermoluminescence techniques are reported. A thermal treatment was introduced to increase the degree of crystallinity. The thermoluminescence glow curve signal of the samples displayed upon exposure to beta radiation was measured and analyzed. It was found that the samples doped with 0.1% of copper and co-doped with 0.3% terbium showed the highest thermoluminescent (TL) signal in response to the irradiated dose. The analyses revealed that the glow curves of the doped samples were composed of nine overlapping glow peaks with activation energies between 0.73 and 2.78 eV. As a whole area under the glow curve, the TL signals displayed a linear dose response in the range from 110 mGy to 55 Gy. The minimum detectible dose of the samples was found to be 10.39 µGy. It was found that peaks 1 and 2 disappear after one day of storage. The rest of the peaks (3-9) remain almost constant up to 74 days of storage.
AU  - El-Faramawy, N.*
AU  - El-Kinawy, M.*
AU  - Farouk, S.*
AU  - Sabry, M.*
AU  - El-Nashar, H.F.*
AU  - Mafodda, A.
AU  - Woda, C.
C1  - 68721
C2  - 54930
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 569-576
TI  - Thermoluminescence characteristics of copper and terbium co-doped lithium tetraborate glass.
JO  - Radiat. Res.
VL  - 200
IS  - 6
PB  - Radiation Research Soc
PY  - 2023
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Recent epidemiological and experimental animal data, as well as reanalyses of data previously accumulated, indicate that the lens of the eye is more radiosensitive than was previously thought. This has resulted in a reduction of the occupational lens dose limit within the European Union countries, Japan and elsewhere. This Commentary introduces the work done by the LDLensRad Consortium contained within this Focus Issue, towards advancement of understanding of the mechanisms of low dose radiation cataract.
AU  - Ainsbury, E.A.*
AU  - Dalke, C.
AU  - Mancuso, M.*
AU  - Kadhim, M.*
AU  - Quinlan, R.A.*
AU  - Azizova, T.*
AU  - Dauer, L.T.*
AU  - Dynlacht, J.R.*
AU  - Tanner, R.*
AU  - Hamada, N.*
C1  - 63646
C2  - 51824
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 1-6
TI  - Introduction to the special LDLensRad focus issue.
JO  - Radiat. Res.
VL  - 197
IS  - 1
PB  - Radiation Research Soc
PY  - 2022
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We have shown previously that a single radiation event (0.063, 0.125 or 0.5 Gy, 0.063 Gy/min) in adult mice (age 10 weeks) can have delayed dose-dependent effects on locomotor behavior 18 months postirradiation. The highest dose (0.5 Gy) reduced, whereas the lowest dose (0.063 Gy) increased locomotor activity at older age independent of sex or genotype. In the current study we investigated whether higher doses administered at a higher dose rate (0.5, 1 or 2 Gy, 0.3 Gy/min) at the same age (10 weeks) cause stronger or earlier effects on a range of behaviors, including locomotion, anxiety, sensorimotor and cognitive behavior. There were clear dose-dependent effects on spontaneous locomotor and exploratory activity, anxiety-related behavior, body weight and affiliative social behavior independent of sex or genotype of wild-type and Ercc2S737P heterozygous mice on a mixed C57BL/6JG and C3HeB/FeJ background. In addition, smaller genotype- and dose-dependent radiation effects on working memory were evident in males, but not in females. The strongest dose-dependent radiation effects were present 4 months postirradiation, but only effects on affiliative social behaviors persisted until 12 months postirradiation. The observed radiation-induced behavioral changes were not related to alterations in the eye lens, as 4 months postirradiation anterior and posterior parts of the lens were still normal. Overall, we did not find any sensitizing effect of the mutation towards radiation effects in vivo.
AU  - Garrett, L.
AU  - Ung, M.-C.
AU  - Einicke, J.
AU  - Zimprich, A.*
AU  - Fenzl, F.*
AU  - Pawliczek, D.
AU  - Graw, J.
AU  - Dalke, C.
AU  - Hölter, S.M.
C1  - 62522
C2  - 50904
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 67-77
TI  - Complex long-term effects of radiation on adult mouse behaviour.
JO  - Radiat. Res.
VL  - 197
IS  - 1
PB  - Radiation Research Soc
PY  - 2022
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Experiments have reported low normal tissue toxicities during FLASH irradiation, but the mechanism has not been elaborated. Several hypotheses have been proposed to explain the mechanism. One hypothesis is oxygen depletion. We analyze the time-dependent change of oxygen concentration in the tissue to study the oxygen depletion hypothesis using a computational model. The effects of physical, chemical and physiological parameters on oxygen depletion were explored. The kinetic equation of the model is solved numerically using the finite difference method with rational boundary conditions. Results of oxygen distribution is supported by the experiments of oxygen-sensitivity electrodes and experiments on the expression and distribution of the hypoxia-inducible factors. The analysis of parameters shows that the steady-state oxygen distribution before irradiation is determined by the oxygen consumption rate of the tissue and the microvessel density. The change of oxygen concentration after irradiation has been found to follow a negative exponential function, and the time constant is mainly determined by the microvessel density. The change of oxygen during exposure increases with dose rate and tends to be saturated because of oxygen diffusion. When the dose rate is high enough, the same dose results in the same reduction of oxygen concentration regardless of dose rate. The analysis of the FLASH effect in the brain tissue based on this model does not support the explanation of the oxygen depletion hypothesis. The oxygen depletion hypothesis remains controversial because the oxygen in most normal tissues cannot be depleted to radiation resistance level by FLASH irradiation.
AU  - Hu, A.*
AU  - Qiu, R.*
AU  - Wu, Z.*
AU  - Zhang, H.*
AU  - Li, W.B.
AU  - Li, J.*
C1  - 63410
C2  - 51524
SP  - 175-183
TI  - A computational model for oxygen depletion hypothesis in FLASH effect.
JO  - Radiat. Res.
VL  - 197
IS  - 2
PY  - 2022
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate. Here, we present the results of a long-term study of changes to lens opacity in male and female adult mice from a variety of different genetic (radiosensitive or radioresistant) backgrounds, including mutant strains Ercc2 and Ptch1, which were assumed to be susceptible to radiation-induced lens opacities. Mice received 0.5, 1 and 2 Gy 60Co gamma-ray irradiation at dose rates of 0.063 and 0.3 Gy min-1. Scheimpflug imaging was used to quantify lens opacification as an early indicator of cataract, with monthly observations taken postirradiation for an 18-month period in all strains apart from 129S2, which were observed for 12 months. Opacification of the lens was found to increase with time postirradiation (with age) for most mouse models, with ionizing radiation exposure increasing opacities further. Sex, dose, dose rate and genetic background were all found to be significant contributors to opacification; however, significant interactions were identified, which meant that the impact of these factors was strain dependent. Mean lens density increased with higher dose and dose rate in the presence of Ercc2 and Ptch1 mutations. This project was the first to focus on low (<1 Gy) dose, multiple dose rate, sex and strain effects in lens opacification, and clearly demonstrates the importance of these experimental factors in radiobiological investigations on the lens. The results provide insight into the effects of ionizing radiation on the lens as well as the need for further work in this area to underpin appropriate radiation protection legislation and guidance.
AU  - McCarron, R.A.*
AU  - Barnard, S.G.R.*
AU  - Babini, G.*
AU  - Dalke, C.
AU  - Graw, J.
AU  - Leonardi, S.*
AU  - Mancuso, M.*
AU  - Moquet, J.E.*
AU  - Pawliczek, D.
AU  - Pazzaglia, S.*
AU  - De Stefano, I.*
AU  - Ainsbury, E.A.*
C1  - 62028
C2  - 50598
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 57-66
TI  - Radiation-induced lens opacity and cataractogenesis: A lifetime study using mice of varying genetic backgrounds.
JO  - Radiat. Res.
VL  - 197
IS  - 1
PB  - Radiation Research Soc
PY  - 2022
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Ionizing radiation is widely known to induce various kinds of lens cataracts, of which posterior subcapsular cataracts (PSCs) have the highest prevalence. Despite some studies regarding the epidemiology and biology of radiation-induced PSCs, the mechanism underscoring the formation of this type of lesions and their dose dependency remain uncertain. Within the current study, our team investigated the in vivo characteristics of PSCs in B6C3F1 mice (F1-hybrids of BL6 × C3H) that received 0.5-2 Gy γ-ray irradiation after postnatal day 70. For purposes of assessing lenticular damages, spectral domain optical coherence tomography was utilized, and the visual acuity of the mice was measured to analyze their levels of visual impairment, and histological sections were then prepared in to characterize in vivo phenotypes. Three varying in vivo phenotype anterior and posterior lesions were thus revealed and correlated with the applied doses to understand their marginal influence on the visual acuity of the studied mice. Histological data indicated no significantly increased odds ratios for PSCs below a dose of 1 Gy at the end of the observation time. Furthermore, our team demonstrated that when the frequencies of the posterior and anterior lesions were calculated at early time points, their responses were in accordance with a deterministic model, whereas at later time points, their responses were better described via a stochastic model. The current study will aid in honing the current understanding of radiation-induced cataract formation and contributes greatly to addressing the fundamental questions of lens dose response within the field of radiation biology.
AU  - Pawliczek, D.
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Hrabě de Angelis, M.
AU  - Quinlan, R.*
AU  - Graw, J.
AU  - Dalke, C.
C1  - 61475
C2  - 50280
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 7-21
TI  - On the nature of murine radiation-induced subcapsular cataracts: Optical coherence tomography-based fine classification, in vivo dynamics and impact on visual acuity.
JO  - Radiat. Res.
VL  - 197
IS  - 1
PB  - Radiation Research Soc
PY  - 2022
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (<2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis. Recently we have reported an inverse dose-rate effect, as well as the low-dose response, of DNA damage and repair in lens epithelial cells (LECs). Here, we present further initial findings from two mutated strains (Ercc2+/- and Ptch1+/-) of mice, both reportedly susceptible to radiation-induced cataract, and their DNA damage and repair response to low-dose and low-dose-rate gamma rays. Our results support the hypothesis that the lens epithelium responds differently to radiation than other tissues, with reported radiation susceptibility to DNA damage not necessarily translating to the LECs. Genetic predisposition and strain(s) of mice have a significant role in radiation-induced cataract susceptibility.
AU  - Barnard, S.G.R.*
AU  - McCarron, R.*
AU  - Mancuso, M.*
AU  - De Stefano, I.*
AU  - Pazzaglia, S.*
AU  - Pawliczek, D.
AU  - Dalke, C.
AU  - Ainsbury, E.A.*
C1  - 61461
C2  - 50270
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 36-42
TI  - Radiation-induced DNA damage and repair in lens epithelial cells of both Ptch1(+/-) and Ercc2(+/-) mutated mice.
JO  - Radiat. Res.
VL  - 197
IS  - 1
PB  - Radiation Research Soc
PY  - 2021
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - With the use of ionizing radiation comes the risk of accidents and malevolent misuse. When unplanned exposures occur, there are several methods which can be used to retrospectively reconstruct individual radiation exposures; biological methods include analysis of aberrations and damage of chromosomes and DNA, while physical methods rely on luminescence (TL/OSL) or EPR signals. To ensure the quality and dependability of these methods, they should be evaluated under realistic exposure conditions. In 2019, EURADOS Working Group 10 and RENEB organized a field test with the purpose of evaluating retrospective dosimetry methods as carried out in potential real-life exposure scenarios. A 1.36 TBq 192Ir source was used to irradiate anthropomorphic phantoms in different geometries at doses of several Gy in an outdoor open-air geometry. Materials intended for accident dosimetry (including mobile phones and blood) were placed on the phantoms together with reference dosimeters (LiF, NaCl, glass). The objective was to estimate radiation exposures received by individuals as measured using blood and fortuitous materials, and to evaluate these methods by comparing the estimated doses to reference measurements and Monte Carlo simulations. Herein we describe the overall planning, goals, execution and preliminary outcomes of the 2019 field test. Such field tests are essential for the development of new and existing methods. The outputs from this field test include useful experience in terms of planning and execution of future exercises, with respect to time management, radiation protection, and reference dosimetry to be considered to obtain relevant data for analysis.
AU  - Waldner, L.*
AU  - Bernhardsson, C.*
AU  - Woda, C.
AU  - Trompier, F.*
AU  - van Hoey, O.*
AU  - Kulka, U.*
AU  - Oestreicher, U.*
AU  - Bassinet, C.*
AU  - Rääf, C.*
AU  - Discher, M.*
AU  - Endesfelder, D.*
AU  - Eakins, J.S.*
AU  - Gregoire, E.*
AU  - Wojcik, A.*
AU  - Ristic, Y.*
AU  - Kim, H.*
AU  - Lee, J.*
AU  - Yu, H.*
AU  - Kim, M.C.*
AU  - Abend, M.*
AU  - Ainsbury, E.*
C1  - 61535
C2  - 50329
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 253-264
TI  - The 2019-2020 EURADOS WG10 and RENEB field test of retrospective dosimetry methods in a small-scale incident involving ionizing radiation.
JO  - Radiat. Res.
VL  - 195
IS  - 3
PB  - Radiation Research Soc
PY  - 2021
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - In the event of a mass casualty radiological or nuclear scenario, it is important to distinguish between the unexposed (worried well), low-dose exposed individuals and those developing the hematological acute radiation syndrome (HARS) within the first three days postirradiation. In previous baboon studies, we identified altered gene expression changes after irradiation, which were predictive for the later developing HARS severity. Similar changes in the expression of four of these genes were observed using an in vitro human whole blood model. However, these studies have provided only limited information on the time frame of the changes after exposure in relationship to the development of HARS. In this study we analyzed the time-dependent changes in mRNA expression after in vitro irradiation of whole blood. Changes in the expression of informative mRNAs (FDXR, DBB2, POU2AF1 and WNT3) were determined in the blood of eight healthy donors (6 males, 2 females) after irradiation at 0 (control), 0.5, 2 and 4 Gy using qRT-PCR. FDXR expression was significantly upregulated (P < 0.001) 4 h after ≥0.5 Gy irradiation, with an 18-40-fold peak attained 4-12 h postirradiation which remained elevated (4-9-fold) at 72 h. DDB2 expression was upregulated after 4 h (fold change, 5-8, P < 0.001 at ≥ 0.5 Gy) and remained upregulated (3-4-fold) until 72 h (P < 0.001). The earliest time points showing a significant downregulation of POU2AF1 and WNT3 were 4 h (fold change = 0.4, P = 0.001, at 4 Gy) and 8 h (fold change = 0.3-0.5, P < 0.001, 2-4 Gy), respectively. These results indicate that the diagnostic window for detecting HARS-predictive changes in gene expression may be opened as early as 2 h for most (75%) and at 4 h postirradiation for all individuals examined. Depending on the RNA species studied this may continue for at least three days postirradiation.
AU  - Ostheim, P.*
AU  - Coker, O.*
AU  - Schüle, S.*
AU  - Hermann, C.*
AU  - Combs, S.E.
AU  - Trott, K.R.*
AU  - Atkinson, M.J.
AU  - Port, M.*
AU  - Abend, M.*
C1  - 60649
C2  - 49560
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 38-46
TI  - Identifying a diagnostic window for the use of gene expression profiling to predict acute radiation syndrome.
JO  - Radiat. Res.
VL  - 195
IS  - 1
PB  - Radiation Research Soc
PY  - 2020
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called ''indirect'' damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.
AU  - Schuemann, J.*
AU  - McNamara, A.L.*
AU  - Warmenhoven, J.W.*
AU  - Henthorn, N.T.*
AU  - Kirkby, K.*
AU  - Merchant, M.J.*
AU  - Ingram, S.*
AU  - Paganetti, H.*
AU  - Held, K.D.*
AU  - Ramos-Mendez, J.*
AU  - Faddegon, B.*
AU  - Perl, J.*
AU  - Goodhead, D.T.*
AU  - Plante, I.*
AU  - Rabus, H.*
AU  - Nettelbeck, H.*
AU  - Friedland, W.
AU  - Kundrát, P.
AU  - Ottolenghi, A.*
AU  - Baiocco, G.*
AU  - Barbieri, S.*
AU  - Dingfelder, M.*
AU  - Incerti, S.*
AU  - Villagrasa, C.*
AU  - Bueno, M.*
AU  - Bernal, M.A.*
AU  - Guatelli, S.*
AU  - Sakata, D.*
AU  - Brown, J.M.C.*
AU  - Francis, Z.*
AU  - Kyriakou, I.*
AU  - Lampe, N.*
AU  - Ballarini, F.*
AU  - Carante, M.P.*
AU  - Davídková, M.*
AU  - Štěpán, V.*
AU  - Jia, X.*
AU  - Cucinotta, F.A.*
AU  - Schulte, R.*
AU  - Stewart, R.D.*
AU  - Carlson, D.J.*
AU  - Galer, S.*
AU  - Kuncic, Z.*
AU  - Lacombe, S.*
AU  - Milligan, J.*
AU  - Cho, S.H.*
AU  - Sawakuchi, G.*
AU  - Inaniwa, T.*
AU  - Sato, T.*
AU  - Li, W.B.
AU  - Solov'yov, A.V.*
AU  - Surdutovich, E.*
AU  - Durante, M.J.*
AU  - Prise, K.M.*
AU  - McMahon, S.J.*
C1  - 54703
C2  - 45772
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 76-92
TI  - A new standard DNA damage (SDD) data format.
JO  - Radiat. Res.
VL  - 191
IS  - 1
PB  - Radiation Research Soc
PY  - 2019
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - In previous studies we determined a gene expression signature in baboons for predicting the severity of hematological acute radiation syndrome. We subsequently validated a set of eight of these genes in leukemia patients undergoing total-body irradiation. In the current study, we addressed the effect of intraindividual variability on the basal level of expression of those eight radiation-responsive genes identified previously, by examining baseline levels in 200 unexposed healthy human donors (122 males and 88 females with an average age of 46 years) using real-time PCR. In addition to the eight candidate genes (DAGLA, WNT3, CD177, PLA2G16, WLS, POU2AF1, STAT4 and PRF1), we examined two more genes (FDXR and DDB2) widely used in ex vivo whole blood experiments. Although significant sex-(seven genes) and age-dependent (two genes) differences in expression were found, the fold changes ranged only between 1.1-1.6. These were well within the twofold differences in gene expression generally considered to represent control values. Age and sex contributed less than 20-30% to the complete inter-individual variance, which is calculated as the fold change between the lowest (reference) and the highest Ct value minimum-maximum fold change (min-max FC). Min-max FCs ranging between 10-17 were observed for most genes; however, for three genes, min-max FCs of complete interindividual variance were found to be 37.1 (WNT3), 51.4 (WLS) and 1,627.8 (CD177). In addition, to determine whether discrimination between healthy and diseased baboons might be altered by replacing the published gene expression data of the 18 healthy baboons with that of the 200 healthy humans, we employed logistic regression analysis and calculated the area under the receiver operating characteristic (ROC) curve. The additional inter-individual variance of the human data set had either no impact or marginal impact on the ROC area, sinceupto 32-fold change gene expression differences between healthy and diseased baboons were observed.
AU  - Agbenyegah, S.*
AU  - Abend, M.*
AU  - Atkinson, M.J.
AU  - Combs, S.E.
AU  - Trott, K.R.*
AU  - Port, M.*
AU  - Majewski, M.*
C1  - 53682
C2  - 44948
CY  - 810 E Tenth Street, Lawrence, Ks 66044 Usa
SP  - 226-235
TI  - Impact of inter-individual variance in the expression of a radiation-responsive gene panel used for triage.
JO  - Radiat. Res.
VL  - 190
IS  - 3
PB  - Radiation Research Soc
PY  - 2018
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - COmputation of Local Electron Release (COOLER), a software program designed for dosimetry assessment at the cellular/subcellular scale, with a given distribution of administered low-energy electron-emitting radionuclides in cellular compartments, which remains a critical step in risk/benefit analysis for advancements in internal radiotherapy. The software is intended to overcome the main limitations of the medical internal radiation dose (MIRD) formalism for calculations of cellular S-values (i.e., dose to a target region in the cell per decay in a given source region), namely, the use of the continuous slowing down approximation (CSDA) and the assumption of a spherical cell geometry. To this aim, we developed an analytical approach, entrusted to a MATLAB-based program, using as input simulated data for electron spatial energy deposition directly derived from full Monte Carlo track structure calculations with PARTRAC. Results from PARTRAC calculations on electron range, stopping power and residual energy versus traveled distance curves are presented and, when useful for implementation in COOLER, analytical fit functions are given. Example configurations for cells in different culture conditions (V79 cells in suspension or adherent culture) with realistic geometrical parameters are implemented for use in the tool. Finally, cellular S-value predictions by the newly developed code are presented for different cellular geometries and activity distributions (uniform activity in the nucleus, in the entire cell or on the cell surface), validated against full Monte Carlo calculations with PARTRAC, and compared to MIRD standards, as well as results based on different track structure calculations (Geant4-DNA). The largest discrepancies between COOLER and MIRD predictions were generally found for electrons between 25 and 30 keV, where the magnitude of disagreement in S-values can vary from 50 to 100%, depending on the activity distribution. In calculations for activity distribution on the cell surface, MIRD predictions appeared to fail the most. The proposed method is suitable for Auger-cascade electrons, but can be extended to any energy of interest and to beta spectra; as an example, the (3)H case is also discussed. COOLER is intended to be accessible to everyone (preclinical and clinical researchers included), and may provide important information for the selection of radionuclides, the interpretation of radiobiological or preclinical results, and the general establishment of doses in any scenario, e.g., with cultured cells in the laboratory or with therapeutic or diagnostic applications. The software will be made available for download from the DTU-Nutech website: http://www.nutech.dtu.dk/ .
AU  - Siragusa, M.*
AU  - Baiocco, G.*
AU  - Fredericia, P.M.*
AU  - Friedland, W.
AU  - Groesser, T.*
AU  - Ottolenghi, A.*
AU  - Jensen, M.*
C1  - 51357
C2  - 43204
CY  - Lawrence
SP  - 204-220
TI  - The COOLER code: A novel analytical approach to calculate subcellular energy deposition by internal electron emitters.
JO  - Radiat. Res.
VL  - 188
IS  - 2
PB  - Radiation Research Soc
PY  - 2017
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.
AU  - Abend, M.*
AU  - Badie, C.*
AU  - Quintens, R.*
AU  - Kriehuber, R.*
AU  - Manning, G.*
AU  - Macaeva, E.*
AU  - Njima, M.*
AU  - Oskamp, D.*
AU  - Strunz, S.*
AU  - Mörtl, S.
AU  - Doucha-Senf, S.*
AU  - Dahlke, S.*
AU  - Menzel, J.*
AU  - Port, M.*
C1  - 47795
C2  - 39508
SP  - 109-123
TI  - Examining radiation-induced in vivo and in vitro gene expression changes of the peripheral blood in different laboratories for biodosimetry purposes: First RENEB gene expression study.
JO  - Radiat. Res.
VL  - 185
IS  - 2
PY  - 2016
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - It has been suggested that a mechanistic understanding of the cellular responses to low dose and dose rate may be valuable in reducing some of the uncertainties involved in current risk estimates for cancer- and non-cancer-related radiation effects that are inherited in the linear no-threshold hypothesis. In this study, the effects of low-dose radiation on the proteome in both human fibroblasts and stem cells were investigated. Particular emphasis was placed on examining: 1. the dose-response relationships for the differential expression of proteins in the low-dose range (40-140 mGy) of low-linear energy transfer (LET) radiation; and 2. the effect on differential expression of proteins of a priming dose given prior to a challenge dose (adaptive response effects). These studies were performed on cultured human fibroblasts (VH10) and human adipose-derived stem cells (ADSC). The results from the VH10 cell experiments demonstrated that low-doses of low-LET radiation induced unique patterns of differentially expressed proteins for each dose investigated. In addition, a low priming radiation dose significantly changed the protein expression induced by the subsequent challenge exposure. In the ADSC the number of differentially expressed proteins was markedly less compared to VH10 cells, indicating that ADSC differ in their intrinsic response to low doses of radiation. The proteomic results are further discussed in terms of possible pathways influenced by low-dose irradiation.
AU  - Hauptmann, M.*
AU  - Haghdoost, S.*
AU  - Gomolka, M.*
AU  - Sarioglu, H.
AU  - Ueffing, M.
AU  - Dietz, A.*
AU  - Kulka, U.*
AU  - Unger, K.
AU  - Babini, G.*
AU  - Harms-Ringdahl, M.*
AU  - Ottolenghi, A.*
AU  - Hornhardt, S.*
C1  - 48039
C2  - 39868
CY  - Lawrence
SP  - 299-312
TI  - Differential response and priming dose effect on the proteome of human fibroblast and stem cells induced by exposure to low doses of ionizing radiation.
JO  - Radiat. Res.
VL  - 185
IS  - 3
PB  - Radiation Research Soc
PY  - 2016
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We examined the association of gene expression with noncancer chronic disease outcomes in Mayak nuclear weapons plant workers who were exposed to radiation due to their occupation. We conducted a cross-sectional study with selection based on radiation exposure status of Mayak plant workers living in Ozyorsk who were alive in 2011 and either exposed to: combined incorporated Plutonium-239 ((239)Pu) and external gamma-ray exposure (n = 82); external gamma-ray exposure alone (n = 18); or were unexposed (n = 50) of Ozyorsk residents who provided community-based professional support for plant personnel and who were alive in 2011. Peripheral blood was taken and RNA was isolated and then converted into cDNA and stored at -20°C. In a previous analysis we screened the whole genome for radiation-associated candidate genes, and validated 15 mRNAs and 15 microRNAs using qRT-PCR. In the current analysis we examined the association of these genes with 15 different chronic diseases on 92 samples (47 males, 45 females). We examined the radiation-to-gene and gene-to-disease associations in statistical models stratified by gender and separately for each disease and exposure. We modeled radiation exposure as gamma or (239)Pu on both the continuous and categorical scales. Unconditional logistic regression was used to calculate odds ratios (OR), 95% confidence intervals (CI), and the concordance for genes that were significantly associated with radiation exposure and a specific disease outcome were identified. Altogether 12 mRNAs and 9 microRNAs appeared to be significantly associated with 6 diseases, including thyroid diseases (3 genes, OR: 1.2-5.1, concordance: 71-78%), atherosclerotic diseases (4 genes, OR: 2.5-10, concordance: 70-75%), kidney diseases (6 genes, OR: 1.3-8.6, concordance: 69-85%), cholelithiasis (3 genes, OR: 0.2-0.3, concordance: 74-75%), benign tumors [1 gene (AGAP4), OR: 3.7, concordance: 81%] and chronic radiation syndrome (4 genes, OR: 2.5-4.3, concordance: 70-99%). Further associations were found for systolic blood pressure (6 genes, OR: 3.7-10.6, concordance: 81-88%) and body mass index [1 gene (miR-484), OR: 3.7, concordance: 81%]. All associations were gender and exposure dependent. These findings suggest that gene expression changes observed after occupational prolonged radiation exposures may increase the risk for certain noncancer chronic diseases.
AU  - Abend, M.*
AU  - Azizova, T.V.*
AU  - Müller, K.*
AU  - Dörr, H.*
AU  - Doucha-Senf, S.*
AU  - Kreppel, H.*
AU  - Rusinova, G.*
AU  - Glazkova, I.*
AU  - Vyazovskaya, N.*
AU  - Unger, K.
AU  - Braselmann, H.
AU  - Meineke, V.*
C1  - 44008
C2  - 36686
CY  - Lawrence
SP  - 249-261
TI  - Association of radiation-induced genes with noncancer chronic diseases in Mayak workers occupationally exposed to prolonged radiation.
JO  - Radiat. Res.
VL  - 183
IS  - 3
PB  - Radiation Research Soc
PY  - 2015
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - A central question in radiation protection research is dose and dose-rate relationship for radiation-induced cardiovascular diseases. The response of endothelial cells to different low dose rates may contribute to help estimate risks for cardiovascular diseases by providing mechanistic understanding. In this study we investigated whether chronic low-dose-rate radiation exposure had an effect on the inflammatory response of endothelial cells and their function. Human umbilical vein endothelial cells (HUVECs) were chronically exposed to radiation at a dose of 1.4 mGy/h or 4.1 mGy/h for 1, 3, 6 or 10 weeks. We determined the pro-inflammatory profile of HUVECs before and during radiation exposure, and investigated the functional consequences of this radiation exposure by measuring their capacity to form vascular networks in matrigel. Expression levels of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and the release of pro-inflammatory cytokines such as MCP-1, IL-6 and TNF-α were analyzed. When a total dose of 2 Gy was given at a rate of 4.1 mGy/h, we observed an increase in IL-6 and MCP-1 release into the cell culture media, but this was not observed at 1.4 mGy/h. The increase in the inflammatory profile induced at the dose rate of 4.1 mGy/h was also correlated with a decrease in the capacity of the HUVECs to form a vascular network in matrigel. Our results suggest that dose rate is an important parameter in the alteration of HUVEC inflammatory profile and function.
AU  - Ebrahimian, T.G.*
AU  - le Gallic, C.*
AU  - Stefani, J.*
AU  - Dublineau, I.*
AU  - Yentrapalli, R.
AU  - Harms-Ringdahl, M.*
AU  - Haghdoost, S.*
C1  - 44793
C2  - 37046
CY  - Lawrence
SP  - 447-454
TI  - Chronic gamma-irradiation induces a dose-rate-dependent pro-inflammatory response and associated loss of function in human umbilical vein endothelial cells.
JO  - Radiat. Res.
VL  - 183
IS  - 4
PB  - Radiation Research Soc
PY  - 2015
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We evaluated gene expression in the peripheral blood of Mayak workers in relationship to occupational chronic exposure to identify permanent post-exposure signatures. The Mayak workers had experienced either a combined exposure to incorporated (239)Pu and external gamma rays (n = 82) or exposure to external gamma rays (n = 18). Fifty unexposed individuals served as controls. Peripheral blood was collected and then the RNA was isolated, converting it into cDNA and stored at -20°C. In a previous study at stage I, we screened the mRNA and microRNA transcriptome using 40 of the 150 samples and identified 95 mRNAs and 45 microRNAs. In stage II of this study, we now validated our 140 candidate genes using the qRT-PCR technique for the remaining 92 blood samples (18 samples were lost due to methodological reasons). We analyzed associations of normalized gene expression values in linear models separately for both exposure types (continuous and categorical scales) and adjusted for exposure age as well as stratified by gender. After further adjustment for confounders such as chronic non-cancer diseases or age at biosampling, mostly binary (on/off) dose-to-gene relationships were found for 15 mRNAs and 15 microRNAs, of which 8 mRNAs and 6 microRNAs remained significant after Bonferroni correction. Almost all of them were associated with plutonium incorporation and gender. Our study provides mRNA and microRNA gene expression changes dependent on the exposure type and gender, which occur and seem to persist after chronic radiation exposures supporting the concept of permanent post-exposure signatures.
AU  - Abend, M.*
AU  - Azizova, T.V.*
AU  - Müller, K.*
AU  - Dörr, H.*
AU  - Senf, S.*
AU  - Kreppel, H.*
AU  - Rusinova, G.*
AU  - Glazkova, I.*
AU  - Vyazovskaya, N.*
AU  - Unger, K.
AU  - Meineke, V.*
C1  - 31900
C2  - 34856
CY  - Lawrence
SP  - 299-309
TI  - Independent validation of candidate genes identified after a whole genome screening on Mayak workers exposed to prolonged occupational radiation.
JO  - Radiat. Res.
VL  - 182
IS  - 3
PB  - Radiation Research Soc
PY  - 2014
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - One of the main issues of low-energy internal emitters concerns the very short ranges of the beta particles, versus the dimensions of the biological targets. Depending on the chemical form, the radionuclide may be more concentrated either in the cytoplasm or in the nucleus of the target cell. Consequently, since in most cases conventional dosimetry neglects this issue it may overestimate or underestimate the dose to the nucleus and hence the biological effects. To assess the magnitude of these deviations and to provide a realistic evaluation of the localized energy deposition by low-energy internal emitters, the biophysical track-structure code PARTRAC was used to calculate nuclear doses, DNA damage yields and fragmentation patterns for different localizations of radionuclides in human interphase fibroblasts. The nuclides considered in the simulations were tritium and nickel-63, which emit electrons with average energies of 5.7 (range in water of 0.42 mu m) and 17 keV (range of 5 mu m), respectively, covering both very short and medium ranges of beta-decay products. The simulation results showed that the largest deviations from the conventional dosimetry occur for inhomogeneously distributed short-range emitters. For uniformly distributed radionuclides selectively in the cytoplasm but excluded from the cell nucleus, the dose in the nucleus is 15% of the average dose in the cell in the case of tritium but 64% for nickel-63. Also, the numbers of double-strand breaks (DSBs) and the distributions of DNA fragments depend on subcellular localization of the radionuclides. In the low-and medium-dose regions investigated here, DSB numbers are proportional to the nuclear dose, with about 50 DSB/Gy for both studied nuclides. In addition, DSB numbers on specific chromosomes depend on the radionuclide localization in the cell as well, with chromosomes located more peripherally in the cell nucleus being more damaged by short-ranged emitters in cytoplasm compared with chromosomes located more centrally. These results illustrate the potential for over- or underestimating the risk associated with low-energy emitters, particularly for tritium intake, when their distribution at subcellular levels is not appropriately considered.
AU  - Alloni, D.*
AU  - Cutaia, C.*
AU  - Mariotti, L.*
AU  - Friedland, W.
AU  - Ottolenghi, A.*
C1  - 32447
C2  - 35036
CY  - Lawrence
SP  - 322-330
TI  - Modeling dose deposition and DNA damage due to low-energy β- emitters.
JO  - Radiat. Res.
VL  - 182
IS  - 3
PB  - Radiation Research Soc
PY  - 2014
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants (134Cs and 137Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in the first year and continuing exposure, the lifetime radiation-related cancer risks based on lifetime dose (which are highest for children under 5 years of age at initial exposure), are small, and much smaller than the lifetime baseline cancer risks. For example, after initial exposure at age 1 year, the lifetime excess radiation risk and baseline risk of all solid cancers in females were estimated to be 0.7 · 10-2 and 29.0 · 10-2, respectively. The 15 year risks based on the lifetime reference dose are very small. However, for initial exposure in childhood, the 15 year risks based on the lifetime reference dose are up to 33 and 88% as large as the 15 year baseline risks for leukemia and thyroid cancer, respectively. The results may be scaled to particular dose estimates after consideration of caveats. One caveat is related to the lack of epidemiological evidence defining risks at low doses, because the predicted risks come from cancer risk models fitted to a wide dose range (0-4 Gy), which assume that the solid cancer and leukemia lifetime risks for doses less than about 0.5 Gy and 0.2 Gy, respectively, are proportional to organ/tissue doses: this is unlikely to seriously underestimate risks, but may overestimate risks. This WHO-HRA framework may be used to update the risk estimates, when new population health statistics data, dosimetry information and radiation risk models become available.
AU  - Walsh, L.*
AU  - Zhang, W.*
AU  - Shore, R.E.*
AU  - Auvinen, A.*
AU  - Laurier, D.*
AU  - Wakeford, R.*
AU  - Jacob, P.
AU  - Gent, N.*
AU  - Anspaugh, L.R.*
AU  - Schüz, J.*
AU  - Kesminiene, A.*
AU  - van Deventer, E.T.*
AU  - Tritscher, A.M.*
AU  - del Rosarion Pérez, M.*
C1  - 42947
C2  - 35892
SP  - 556-572
TI  - A framework for estimating radiation-related cancer risks in Japan from the 2011 Fukushima nuclear accident.
JO  - Radiat. Res.
VL  - 182
IS  - 5
PY  - 2014
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The number of small radiation-induced DNA fragments can be heavily underestimated when determined from measurements of DNA mass fractions by gel electrophoresis, leading to a consequent underestimation of the initial DNA damage induction. In this study we reanalyzed the experimental results for DNA fragmentation and DNA double-strand break (DSB) yields in human fibroblasts irradiated with γ rays and nitrogen ion beams with linear energy transfer (LET) equal to 80, 125, 175 and 225 keV/μm, originally measured by Höglund et al. (Radiat Res 155, 818-825, 2001 and Int J Radiat Biol 76, 539-547, 2000). In that study the authors converted the measured distributions of fragment masses into DNA fragment distributions using mid-range values of the measured fragment length intervals, in particular they assumed fragments with lengths in the interval of 0-48 kbp had the mid-range value of 24 kbp. However, our recent detailed simulations with the Monte Carlo code PARTRAC, while reasonably in agreement with the mass distributions, indicate significantly increased yields of very short fragments by high-LET radiation, so that the actual average fragment lengths, in the interval 0-48 kbp, 2.4 kbp for 225 keV/μm nitrogen ions were much shorter than the assumed mid-range value of 24 kbp. When the measured distributions of fragment masses are converted into fragment distributions using the average fragment lengths calculated by PARTRAC, significantly higher yields of DSB related to short fragments were obtained and resulted in a constant relative biological effectiveness (RBE) for DSB induction yield of 2.3 for nitrogen ions at 125-225 keV/μm LET. The previously reported downward trend of the RBE values over this LET range for DSB induction appears to be an artifact of an inadequate average fragment length in the smallest interval.
AU  - Alloni, D.*
AU  - Campa, A.*
AU  - Friedland, W.
AU  - Mariotti, L.*
AU  - Ottolenghi, A.*
C1  - 26072
C2  - 32055
CY  - Lawrence
SP  - 690-697
TI  - Integration of Monte Carlo simulations with PFGE experimental data yields constant RBE of 2.3 for DNA double-strand break induction by nitrogen ions between 125 and 225 keV/μm LET.
JO  - Radiat. Res.
VL  - 179
IS  - 6
PB  - Radiation Research Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The possibility of a large-scale acute radiation exposure necessitates the development of new methods that could provide rapid individual dose estimates with high sample throughput. The focus of the study was an intercomparison of laboratories' dose-assessment performances using gene expression assays. Lithium-heparinized whole blood from one healthy donor was irradiated (240 kVp, 1 Gy/min) immediately after venipuncture at approximately 37°C using single X-ray doses. Blood samples to establish calibration curves (0.25-4 Gy) as well as 10 blinded test samples (0.1-6.4 Gy) were incubated for 24 h at 37°C supplemented with an equal volume of medium and 10% fetal calf serum. For quantitative reverse transcription polymerase chain reaction (qRT-PCR), samples were lysed, stored at -20°C and shipped on ice. For the Chemical Ligation Dependent Probe Amplification methodology (CLPA), aliquots were incubated in 2 ml CLPA reaction buffer (DxTerity), mixed and shipped at room temperature. Assays were run in each laboratory according to locally established protocols. The mean absolute difference (MAD) of estimated doses relative to the true doses (in Gy) was calculated. We also merged doses into binary categories reflecting aspects of clinical/diagnostic relevance and examined accuracy, sensitivity and specificity. The earliest reported time on dose estimates was <8 h. The standard deviation of technical replicate measurements in 75% of all measurements was below 11%. MAD values of 0.3-0.5 Gy and 0.8-1.3 Gy divided the laboratories contributions into two groups. These fourfold differences in accuracy could be primarily explained by unexpected variances of the housekeeping gene (P = 0.0008) and performance differences in processing of calibration and blinded test samples by half of the contributing laboratories. Reported gene expression dose estimates aggregated into binary categories in general showed an accuracies and sensitivities of 93-100% and 76-100% for the groups, with low MAD and high MAD, respectively. In conclusion, gene expression-based dose estimates were reported quickly, and for laboratories with MAD between 0.3-0.5 Gy binary dose categories of clinical significance could be discriminated with an accuracy and sensitivity comparable to established cytogenetic assays.
AU  - Badie, C.*
AU  - Kabacik, S.*
AU  - Balagurunathan, Y.*
AU  - Bernard, N.*
AU  - Brengues, M.*
AU  - Faggioni, G.*
AU  - Greither, R.*
AU  - Lista, F.*
AU  - Peinnequin, A.*
AU  - Poyot, T.*
AU  - Herodin, F.*
AU  - Missel, A.*
AU  - Terbrueggen, B.*
AU  - Zenhausern, F.*
AU  - Rothkamm, K.*
AU  - Meineke, V.*
AU  - Braselmann, H.
AU  - Beinke, C.*
AU  - Abend, M.*
C1  - 27391
C2  - 32646
CY  - Lawrence
SP  - 138-148
TI  - Laboratory intercomparison of gene expression assays.
JO  - Radiat. Res.
VL  - 180
IS  - 2
PB  - Radiation Research Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The study design and obtained results represent an intercomparison of various laboratories performing dose assessment using the dicentric chromosome analysis (DCA) as a diagnostic triage tool for individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-5 Gy) as well as blind samples (0.1-6.4 Gy) were sent to the participants. DCA was performed according to established protocols. The time taken to report dose estimates was documented for each laboratory. Additional information concerning laboratory organization/characteristics as well as assay performance was collected. The mean absolute difference (MAD) was calculated and radiation doses were merged into four triage categories reflecting clinical aspects to calculate accuracy, sensitivity and specificity. The earliest report time was 2.4 days after sample arrival. DCA dose estimates were reported with high and comparable accuracy, with MAD values ranging between 0.16-0.5 Gy for both manual and automated scoring. No significant differences were found for dose estimates based either on 20, 30, 40 or 50 cells, suggesting that the scored number of cells can be reduced from 50 to 20 without loss of precision of triage dose estimates, at least for homogenous exposure scenarios. Triage categories of clinical significance could be discriminated efficiently using both scoring procedures.
AU  - Beinke, C.*
AU  - Barnard, S.*
AU  - Boulay-Greene, H.*
AU  - de Amicis, A.*
AU  - de Sanctis, S.*
AU  - Herodin, F.*
AU  - Jones, A.*
AU  - Kulka, U.*
AU  - Lista, F.*
AU  - Lloyd, D.*
AU  - Martigne, P.*
AU  - Moquet, J.*
AU  - Oestreicher, U.*
AU  - Romm, H.*
AU  - Rothkamm, K.*
AU  - Valente, M.*
AU  - Meineke, V.*
AU  - Braselmann, H.
AU  - Abend, M.*
C1  - 27397
C2  - 32649
CY  - Lawrence
SP  - 129-137
TI  - Laboratory intercomparison of the dicentric chromosome analysis assay.
JO  - Radiat. Res.
VL  - 180
IS  - 2
PB  - Radiation Research Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Medulloblastomas in Patched heterozygous mice (Ptc1(+/-) mice) are induced with high probability by ionizing radiation applied in the immediate post-natal period. A mathematical model is described here that accommodates the dependence of the medulloblastoma incidence on dose, age at exposure and age. The model assumes that the first step in the development of the cancer is already present in all cells of the patched mouse due to germ-line inactivation of one allele of the patched tumor suppressor gene. The subsequent rate-limiting step is dependent linearly on dose at least up to 3 Gy. The observed strong decrease in carcinogenic effect of radiation between exposure on day 1 and day 10 is described by a physiological elimination of target cells during post-natal maturation of the brain. A single malignant cell develops into a tumor following a gamma-distribution with mean of about 160 days. The multiplicity of medulloblastomas is predicted.
AU  - Heidenreich, W.F.
AU  - Saran, A.*
AU  - Atkinson, M.J.
AU  - Pazzaglia, S.*
C1  - 26152
C2  - 32095
CY  - Lawrence
SP  - 610-614
TI  - A mechanistic model for medulloblastoma induction in mice.
JO  - Radiat. Res.
VL  - 179
IS  - 5
PB  - Radiation Research Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The focus of the study is an intercomparison of laboratories' dose-assessment performances using the cytokinesis-block micronucleus (CBMN) assay as a diagnostic triage tool for individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-5 Gy) as well as blind samples (0.1-6.4 Gy) were sent to the participants. The CBMN assay was performed according to protocols individually established and varying among participating laboratories. The time taken to report dose estimates was documented for each laboratory. Additional information concerning laboratory organization/characteristics as well as assay performance was collected. The mean absolute difference (MAD) was calculated and radiation doses were merged into four triage categories reflecting clinical aspects to calculate accuracy, sensitivity and specificity. The earliest report time was 4 days after sample arrival. The CBMN dose estimates were reported with high accuracy (MAD values of 0.20-0.50 Gy at doses below 6.4 Gy for both manual and automated scoring procedures), but showed a limitation of the assay at the dose point of 6.4 Gy, which resulted in a clear dose underestimation in all cases. The MAD values (without 6.4 Gy) differed significantly (P = 0.03) between manual (0.25 Gy, SEM = 0.06, n = 4) or automated scoring procedures (0.37 Gy, SEM = 0.08, n = 5), but lowest MAD were equal (0.2 Gy) for both scoring procedures. Likewise, both scoring procedures led to the same allocation of dose estimates to triage categories of clinical significance (about 83% accuracy and up to 100% specificity).
AU  - Romm, H.*
AU  - Barnard, S.*
AU  - Boulay-Greene, H.*
AU  - de Amicis, A.*
AU  - de Sanctis, S.*
AU  - Franco, M.*
AU  - Herodin, F.*
AU  - Jones, A.*
AU  - Kulka, U.*
AU  - Lista, F.*
AU  - Martigne, P.*
AU  - Moquet, J.*
AU  - Oestreicher, U.*
AU  - Rothkamm, K.*
AU  - Thierens, H.*
AU  - Valente, M.*
AU  - Vandersickel, V.*
AU  - Vral, A.*
AU  - Braselmann, H.
AU  - Meineke, V.*
AU  - Abend, M.*
AU  - Beinke, C.*
C1  - 27393
C2  - 32647
CY  - Lawrence
SP  - 120-128
TI  - Laboratory intercomparison of the cytokinesis-block micronucleus assay.
JO  - Radiat. Res.
VL  - 180
IS  - 2
PB  - Radiation Research Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The focus of the study is an intercomparison of laboratories' dose-assessment performances using the γ-H2AX foci assay as a diagnostic triage tool for rapid individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-4 Gy) as well as blinded test samples (0.1-6.4 Gy) were incubated at 37°C for 2 and 24 h (repair time) and sent to the participants. The foci assay was performed according to protocols individually established in participating laboratories and therefore varied. The time taken to report dose estimates was documented for each laboratory. Additional information concerning laboratory organization/characteristics as well as assay performance was collected. The mean absolute difference (MAD) of estimated doses relative to the actual doses was calculated and radiation doses were merged into four triage categories reflecting clinical relevance to calculate accuracy, sensitivity and specificity. First γ-H2AX based dose estimates were reported 7 h after sample receipt. Estimates were similarly accurate for 2 and 24 h repair times, providing scope for its use in the early phase of a radiation exposure incident. Equal accuracy was achieved by scoring 20, 30, 40 or 50 cells per sample. However, MAD values of 0.5-0.7 Gy and 1.3-1.7 Gy divided the data sets into two groups, driven mainly by the considerable differences in foci yields between calibration and blind samples. Foci yields also varied dramatically between laboratories, highlighting reproducibility issues as an important caveat of the foci assay. Nonetheless, foci counts could distinguish high- and low-dose samples in all data sets and binary dose categories of clinical significance could be discriminated with satisfactory accuracy (mean 84%, ±0.03 SEM). Overall, the results suggest that the γ-H2AX assay is a useful tool for rapidly screening individuals for significant exposures that occurred up to at least 24 h earlier, and may help to prioritize cytogenetic dosimetry follow-up.
AU  - Rothkamm, K.*
AU  - Horn, S.*
AU  - Scherthan, H.*
AU  - Rößler, U.*
AU  - de Amicis, A.*
AU  - Barnard, S.*
AU  - Kulka, U.*
AU  - Lista, F.*
AU  - Meineke, V.*
AU  - Braselmann, H.
AU  - Beinke, C.*
AU  - Abend, M.*
C1  - 27389
C2  - 32645
CY  - Lawrence
SP  - 149-155
TI  - Laboratory intercomparison on the γ-H2AX foci assay.
JO  - Radiat. Res.
VL  - 180
IS  - 2
PB  - Radiation Res. Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools.
AU  - Rothkamm, K.*
AU  - Beinke, C.*
AU  - Romm, H.*
AU  - Badie, C.*
AU  - Balagurunathan, Y.*
AU  - Barnard, S.*
AU  - Bernard, N.*
AU  - Boulay-Greene, H.*
AU  - Brengues, M.*
AU  - de Amicis, A.*
AU  - de Sanctis, S.*
AU  - Greither, R.*
AU  - Herodin, F.*
AU  - Jones, A.*
AU  - Kabacik, S.*
AU  - Knie, T.*
AU  - Kulka, U.*
AU  - Lista, F.*
AU  - Martigne, P.*
AU  - Missel, A.*
AU  - Moquet, J.*
AU  - Oestreicher, U.*
AU  - Peinnequin, A.*
AU  - Poyot, T.*
AU  - Roessler, U.*
AU  - Scherthan, H.*
AU  - Terbrueggen, B.*
AU  - Thierens, H.*
AU  - Valente, M.*
AU  - Vral, A.*
AU  - Zenhausern, F.*
AU  - Meineke, V.*
AU  - Braselmann, H.
AU  - Abend, M.*
C1  - 27395
C2  - 32648
CY  - Lawrence
SP  - 111-119
TI  - Comparison of established and emerging biodosimetry assays.
JO  - Radiat. Res.
VL  - 180
IS  - 2
PB  - Radiation Research Soc.
PY  - 2013
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - For financial and ethical reasons, the large-scale radiobiological animal studies conducted over the past 50 years are, to a large extent, unrepeatable experiments. It is therefore important to retain the primary data from these experiments to allow reanalysis, reinterpretation and re-evaluation of results from, for example, carcinogenicity studies, in the light of new knowledge in radiation biology. Consequently, there is an imperative need to keep these data available for the research community. The European Radiobiological Archives (ERA) were developed to fulfill this task. ERA has become a unique archive, including information from almost all European long-term studies carried out between the 1960s and the 1990s. The legacy database was originally developed in a manner that precluded online use. Therefore, strong efforts were made to transform it into a version that is available online through the web. This went together with quality assurance measures, including first the estimation of the rate of non-systematic errors in data entry, which at 2% proved to be very low. Second, every data set was compared against two external sources of information. Standardization of terminology and histopathology is a prerequisite for meaningful comparison of data across studies and analysis of potential carcinogenic effects. Standardization is particularly critical for the construction of a database that includes data from different studies evaluated by pathologists in different laboratories. A harmonized pathology nomenclature with modern standard pathology terms was introduced. As far as possible, references for the various studies were directly linked to the studies themselves. Further, a direct link to the JANUS database was established. ERA is now in a position where it has the potential to become a worldwide radiobiological research tool. ERA can be accessed at no cost at https://era.bfs.de . An ID and password can be obtained from the curators at era@bfs.de .
AU  - Birschwilks, M.*
AU  - Gruenberger, M.*
AU  - Adelmann, C.*
AU  - Tapio, S.
AU  - Gerber, G.*
AU  - Schofield, P.N.*
AU  - Grosche, B.*
C1  - 5040
C2  - 28447
CY  - Lawrence, KS
SP  - 526-531
TI  - The European radiobiological archives: Online access to data from radiobiological experiments.
JO  - Radiat. Res.
VL  - 175
IS  - 4
PB  - Radiation Research Soc.
PY  - 2011
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - High-linear energy transfer (LET) ion irradiation of cell nuclei induces complex and severe DNA lesions, and foci of repair proteins are formed densely along the ion trajectory. To efficiently discriminate the densely distributed/overlapping foci along the ion trajectory, a focus recognition algorithm called FociPicker3D based on a local fraction thresholding technique was developed. We analyzed high-resolution 3D immunofluorescence microscopic focus images and obtained the kinetics and spatial development of γ-H2AX, 53BP1 and phospho-NBS1 foci in BJ1-hTERT cells irradiated with 55 MeV carbon ions and compared the results with the dynamics of double-strand break (DSB) distributions simulated using the PARTRAC model. Clusters consisting of several foci were observed along the ion trajectory after irradiation. The spatial dynamics of the protein foci supports that the foci clusters are not formed by neighboring foci but instead originate from the DSB cluster damage induced by high-LET radiations.
AU  - Du, G.*
AU  - Drexler, G.A.
AU  - Friedland, W.
AU  - Greubel, C.*
AU  - Hable, V.*
AU  - Krücken, R.*
AU  - Kugler, A.*
AU  - Tonelli, L.*
AU  - Friedl, A.A.*
AU  - Dollinger, G.*
C1  - 6853
C2  - 29356
SP  - 706-715
TI  - Spatial dynamics of DNA damage response protein foci along the ion trajectory of high-LET particles.
JO  - Radiat. Res.
VL  - 176
IS  - 6
PB  - Radiation Research Society
PY  - 2011
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - A detailed understanding of the mechanisms that determine the variable cellular sensitivity to radiation is needed for improved radiation therapy as well as for the identification of individuals with innate radiation hypersensitivity. MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate protein expression. Alterations in miRNA expression patterns in response to ionizing radiation have been shown, but there are almost no data describing the functional impact of these miRNA changes. We report here the results of studies on the functional roles of miRNAs in the radiation response in immortalized and primary endothelial cells. Global suppression of miRNA expression was achieved through downregulation of Argonaut e-2 (AGO2) or DICER proteins using RNAi. The reductions in either DICER or AGO2 led to increased cell death after irradiation, indicating a prosurvival function of miRNAs. Furthermore, while cell cycle checkpoint activation and apoptosis were compromised, DNA double-strand break repair was not affected by the lack of miRNAs. The differential sensitivity of these pathways implies the independent activation of the two response pathways rather than a concerted DNA damage response. The miRNAs that were changed after 2.5 Gy irradiation were identified by TaqMan-based low-density array technology. Of the miRNAs showing an upregulation 4 h or 24 h after radiation exposure, we were able to establish prosurvival and antiapoptotic functions for three miRNAs. Taken together, our data indicate a general prosurvival role for miRNA-mediated gene regulation during the radiation response. We show a functional association between miRNAs, apoptosis and cell cycle checkpoint activation in irradiated cells.
AU  - Krämer, A.
AU  - Anastasov, N.
AU  - Angermeier, M.
AU  - Winkler, K.
AU  - Atkinson, M.J.
AU  - Mörtl, S.
C1  - 6253
C2  - 29063
SP  - 575-586
TI  - MicroRNA-mediated processes are essential for the cellular radiation response.
JO  - Radiat. Res.
VL  - 176
IS  - 5
PB  - Radiation Res. Soc.
PY  - 2011
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We simulated the irradiation of human fibroblasts with gamma rays, protons and helium, carbon and iron ions at a fixed dose of 5 Gy. The simulations were performed with the biophysical Monte Carlo code PARTRAC. From the output of the code, containing in particular the genomic positions of the radiation-induced DNA double-strand breaks (DSBs), we obtained the DNA fragmentation spectra. Very small fragments, in particular those related to "complex lesions" (few tens of base pairs), are probably very important for the late cellular consequences, but their detection is not possible with the common experimental techniques. We paid special attention to the differences among the various ions in the production of these very small fragments; in particular, we compared the fragmentation spectra for ions of the same specific energy and for ions of the same LET (linear energy transfer). As found previously for iron ions, we found that the RBE (relative biological effectiveness) for DSB production was considerably higher than 1 for all high-LET radiations considered. This is at variance with the results obtainable from experimental data, and it is due to the ability to count the contribution of small fragments. It should be noted that for a given LET this RBE decreases with increasing ion charge, due mainly to the increasing mean energy of secondary electrons. A precise quantification of the DNA initial damage can be of great importance for both radiation protection, particularly in open-space long-term manned missions, and hadrontherapy.
AU  - Alloni, D.*
AU  - Campa, A.*
AU  - Belli, M.*
AU  - Esposito, G.*
AU  - Facoetti, A.*
AU  - Friedland, W.
AU  - Liotta, M.*
AU  - Mariotti, L.*
AU  - Paretzke, H.G.
AU  - Ottolenghi, A.*
C1  - 2715
C2  - 27518
SP  - 263-271
TI  - A Monte Carlo study of the radiation quality dependence of DNA fragmentation spectra.
JO  - Radiat. Res.
VL  - 173
IS  - 3
PB  - Radiation Research Society
PY  - 2010
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - A Monte Carlo simulation model for DNA repair via the non-homologous end-joining pathway has been developed. Initial DNA damage calculated by the Monte Carlo track structure code PARTRAC provides starting conditions concerning spatial distribution of double-strand breaks (DSBs) and characterization of lesion complexity. DNA termini undergo attachment and dissociation of repair enzymes described in stochastic first-order kinetics as well as step-by-step diffusive motion considering nuclear attachment sites. Pairs of DNA termini with attached DNA-PK enter synapsis under spatial proximity conditions. After synapsis, a single rate-limiting step is assumed for clean DNA ends, and step-by-step removal of nearby base lesions and strand breaks is considered for dirty DNA ends. Four simple model scenarios reflecting different hypotheses on the origin of the slow phase of DSB repair have been set up. Parameters for the presynaptic phase have been derived from experimental data for Ku70/Ku80 and DNA-PK association and dissociation kinetics. Time constants for the post-synaptic phase have been adapted to experimental DSB rejoining kinetics for human fibroblasts after (137)Cs gamma irradiation. In addition to DSB rejoining kinetics, the yields of residual DSBs, incorrectly rejoined DSBs, and chromosomal aberrations have been determined as a function of dose and compared with experimental data. Three of the model scenarios obviously overestimate residual DSBs after long-term repair after low-dose irradiation, whereas misrejoined DSBs and chromosomal aberrations are in surprisingly good agreement with measurements.
AU  - Friedland, W.
AU  - Jacob, P.
AU  - Kundrát, P.
C1  - 2206
C2  - 27517
SP  - 677-688
TI  - Stochastic simulation of DNA double-strand break repair by non-homologous end joining based on track structure calculations.
JO  - Radiat. Res.
VL  - 173
IS  - 5
PB  - Radiation Research Society
PY  - 2010
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Ron, E.*
AU  - Jacob, P.
C1  - 5373
C2  - 28397
SP  - 789-792
TI  - Late health effects of ionizing radiation: Bridging the experimental and epidemiologic divide.
JO  - Radiat. Res.
VL  - 174
IS  - 6
PB  - Radiation Research Soc
PY  - 2010
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - (41)Ca is produced mainly by absorption of low-energy neutrons on stable (40)Ca. We used accelerator mass spectrometry (AMS) to measure (41)Ca in enamel of 16 teeth from 13 atomic bomb survivors who were exposed to the bomb within 1.2 km from the hypocenter in Hiroshima. In our accompanying paper (Wallner et al., Radiat. Res. 174, 000-000, 2010), we reported that the background-corrected (41)Ca/Ca ratio decreased from 19.5 x 10(-15) to 2.8 x 10(-15) with increasing distance from the hypocenter. Here we show that the measured ratios are in good correlation with gamma-ray doses assessed by electron paramagnetic resonance (EPR) in the same enamel samples, and agree well with calculated ratios based on either the current Dosimetry System 2002 (DS02) or more customized dose estimates where the regression slope as obtained from an errors-in-variables linear model was about 0.85. The calculated DS02 neutron dose to the survivors was about 10 to 80 mGy. The low-energy neutrons responsible for (41)Ca activation contributed variably to the total neutron dose depending on the shielding conditions. Namely, the contribution was smaller (10%) when shielding conditions were lighter (e.g., outside far away from a single house) and was larger (26%) when they were heavier (e.g., in or close to several houses) because of local moderation of neutrons by shielding materials. We conclude that AMS is useful for verifying calculated neutron doses under mixed exposure conditions with gamma rays.
AU  - Rühm, W.
AU  - Wallner, A.*
AU  - Cullings, H.*
AU  - Egbert, S.D.*
AU  - El-Faramawy, N.
AU  - Faestermann, T.*
AU  - Kaul, D.*
AU  - Knie, K.*
AU  - Korschinek, G.*
AU  - Nakamura, N.*
AU  - Roberts, J.*
AU  - Rugel, G.*
C1  - 6066
C2  - 27815
SP  - 146-154
TI  - ⁴¹Ca in tooth enamel. Part II: A means for retrospective biological neutron dosimetry in atomic bomb survivors.
JO  - Radiat. Res.
VL  - 174
IS  - 2
PB  - Radiation Research Society
PY  - 2010
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The detection of (41)Ca atoms in tooth enamel using accelerator mass spectrometry is suggested as a method capable of reconstructing thermal neutron exposures from atomic bomb survivors in Hiroshima and Nagasaki. In general, (41)Ca atoms are produced via thermal neutron capture by stable (40)Ca. Thus any (41)Ca atoms present in the tooth enamel of the survivors would be due to neutron exposure from both natural sources and radiation from the bomb. Tooth samples from five survivors in a control group with negligible neutron exposure were used to investigate the natural (41)Ca content in tooth enamel, and 16 tooth samples from 13 survivors were used to estimate bomb-related neutron exposure. The results showed that the mean (41)Ca/Ca isotope ratio was (0.17 +/- 0.05) x 10(-14) in the control samples and increased to 2 x 10(-14) for survivors who were proximally exposed to the bomb. The (41)Ca/Ca ratios showed an inverse correlation with distance from the hypocenter at the time of the bombing, similar to values that have been derived from theoretical free-in-air thermal-neutron transport calculations. Given that gamma-ray doses were determined earlier for the same tooth samples by means of electron spin resonance (ESR, or electron paramagnetic resonance, EPR), these results can serve to validate neutron exposures that were calculated individually for the survivors but that had to incorporate a number of assumptions (e.g. shielding conditions for the survivors).
AU  - Wallner, A.*
AU  - Rühm, W.
AU  - Rugel, G.*
AU  - Nakamura, N.*
AU  - Arazi, A.*
AU  - Faestermann, T.*
AU  - Knie, K.*
AU  - Maier, H.J.*
AU  - Korschinek, G.*
C1  - 2302
C2  - 27370
SP  - 137-145
TI  - ⁴¹Ca in tooth enamel. Part I: A biological signature of neutron exposure in atomic bomb survivors.
JO  - Radiat. Res.
VL  - 174
IS  - 2
PB  - Radiaton Research Society
PY  - 2010
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and it is known that cataracts can be induced by acute doses of less than 2 Gy of low-LET ionizing radiation and less than 5 Gy of protracted radiation. Although much work has been carried out in this area, the exact mechanisms of radiation cataractogenesis are still not fully understood. In particular, the question of the threshold dose for cataract development is not resolved. Cataracts have been classified as a deterministic effect of radiation exposure with a threshold of approximately 2 Gy. Here we review the combined results of recent mechanistic and human studies regarding induction of cataracts by ionizing radiation. These studies indicate that the threshold for cataract development is certainly less than was previously estimated, of the order of 0.5 Gy, or that radiation cataractogenesis may in fact be more accurately described by a linear, no-threshold model.
AU  - Ainsbury, E.A.*
AU  - Bouffler, S.D.*
AU  - Dörr, W.*
AU  - Graw, J.
AU  - Muirhead, C.R.*
AU  - Edwards, A.A.*
AU  - Cooper, J.*
C1  - 1642
C2  - 26967
SP  - 1-9 
TI  - Radiation cataractogenesis: A review of recent studies.
JO  - Radiat. Res.
VL  - 172
IS  - 1
PB  - Radiation Research Soc
PY  - 2009
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We studied the DNA fragmentation induced in human fibroblasts by iron-ion beams of two different energies: 115 MeV/nucleon and 414 MeV/nucleon. Experimental data were obtained in the fragment size range 1-5700 kbp; Monte Carlo simulations were performed with the PARTRAC code; data analysis was also performed through the Generalized Broken Stick (GBS) model. The comparison between experimental and simulated data for the number of fragments produced in two different size ranges, 1-23 kbp and 23-5700 kbp, gives a satisfactory agreement for both radiation qualities. The Monte Carlo simulations also allow the counting of fragments outside the experimental range: The number of fragments smaller than 1 kbp is large for both beams, although with a strong difference between the two cases. As a consequence, we can compute different RBEs depending on the size range considered for the fragment counting. The PARTRAC evaluation takes into account fragments of all sizes, while the evaluation from the experimental data considers only the fragments in the range of 1-5700 kbp. When the PARTRAC evaluation is restricted to this range, the agreement between experimental and computed RBE values is again good. When fragments smaller than 1 kbp are also considered, the RBE increases considerably, since gamma rays produce a small number of such fragments. The analysis performed with the GBS model proved to be quite sensitive to showing, with a phenomenological single parameter, variations in double-strand break (DSB) correlation.
AU  - Campa, A.
AU  - Alloni, D.
AU  - Antonelli, E.
AU  - Ballarini, E.
AU  - Belli, M.
AU  - Dini, V.
AU  - Esposito, G.
AU  - Facoetti, A.
AU  - Friedland, W.
AU  - Furusawa, Y.
AU  - Liotta, M.
AU  - Ottolenghi, A.
AU  - Paretzke, H.G.
AU  - Simone, G.
AU  - Sorrentino, E.
AU  - Tabocchini, M.A.
C1  - 300
C2  - 26296
SP  - 438-445
TI  - DNA fragmentation induced in human fibroblasts by ⁵⁶Fe ions: Experimental data and Monte Carlo simulations.
JO  - Radiat. Res.
VL  - 171
IS  - 4
PB  - Radiation Research Soc
PY  - 2009
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Ionizing radiation is an established cause of cancer, yet little is known about the health effects of doses from diagnostic examinations in children. The risk of childhood cancer was studied in a cohort of 92.957 children who had been examined with diagnostic X rays in a large German hospital during 1976-2003. Radiation doses were reconstructed using the individual dose area product and other exposure parameters, together with conversion coefficients developed specifically for the medical devices and standards used at the radiology department. Newly diagnosed cancers occurring between 1980 and 2006 were determined through record linkage to the German Childhood Cancer Registry. The median radiation dose was 7 mu Sv. Eight-seven incident cases were found in the cohort: 33 leukemia, 13 lymphoma, 10 central nervous system tumors, and 31 other tumors. The standardized incidence ratio (SIR) for all cancers was 0.99 (95% CI: 0.79-1.22). No trend in the incidence of total cancer, leukemia or solid tumors with increasing radiation dose was observed in the SIR analysis or in the multivariate Poisson regression. Risk did not differ significantly in girls and boys. Overall, while no increase in cancer risk with diagnostic radiation was observed, the results are compatible with a broad range of risk estimates.
AU  - Hammer, G.P.*
AU  - Seidenbusch, M.C.*
AU  - Schneider, K.*
AU  - Regulla, D.F.
AU  - Zeeb, H.*
AU  - Spix, C.*
AU  - Blettner, M.*
C1  - 946
C2  - 26249
SP  - 504-512
TI  - A cohort study of childhood cancer incidence after postnatal diagnostic X-ray exposure.
JO  - Radiat. Res.
VL  - 171
IS  - 4
PB  - Radiation Research Soc
PY  - 2009
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The first measurements of (63)Ni produced by A-bomb fast neutrons (above approximately 1 MeV) in copper samples from Hiroshima encompassed distances from approximately 380 to 5062 m from the hypocenter (the point on the ground directly under the bomb). They included the region of interest to survivor studies (approximately 900 to 1500 m) and provided the first direct validation of fast neutrons in that range. However, a significant measurement gap remained between the hypocenter and 380 m. Measurements close to the hypocenter are important as a high-value anchor for the slope of the curve for neutron activation as a function of distance. Here we report measurements of (63)Ni in copper samples from the historic Hiroshima Atomic Bomb Dome, which is located approximately 150 m from the hypocenter. These measurements extend the range of our previously published data for (63)Ni providing a more comprehensive and consistent A-bomb activation curve. The results are also in good agreement with calculations based on the current dosimetry system (DS02) and give further experimental support to the accuracy of this system that forms the basis for radiation risk estimates worldwide.
AU  - Marchetti, A.A.*
AU  - McAninch, J.E.*
AU  - Rugel, G.*
AU  - Rühm, W.
AU  - Korschinek, G.*
AU  - Martinelli, R.E.*
AU  - Faestermann, T.*
AU  - Knie, K.*
AU  - Egbert, S.D.*
AU  - Wallner, A.*
AU  - Wallner, C.*
AU  - Tanaka, K.*
AU  - Endo, S.*
AU  - Hoshi, M.*
AU  - Shizuma, K.*
AU  - Fujita, S.*
AU  - Hasai, H.*
AU  - Imanaka, T.*
AU  - Straume, T.*
C1  - 500
C2  - 25860
SP  - 118-122
TI  - Fast neutrons measured in copper from the Hiroshima atomic bomb dome.
JO  - Radiat. Res.
VL  - 171
IS  - 1
PB  - Radiation Research Soc
PY  - 2009
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Two recent studies analyzed thyroid cancer incidence in Belarus and Ukraine during the period from 1990 to 2001, for the birth cohort 1968 to 1985, and the related (131)I exposure associated with the Chernobyl accident in 1986. Contradictory age-at-exposure and time-since-exposure effect modifications of the excess relative risk (ERR) were reported. The present study identifies the choice of baseline modeling method as the reason for the conflicting results. Various quality-of-fit criteria favor a parametric baseline model to various categorical baseline models. The model with a parametric baseline results in a decrease of the ERR by a factor of about 0.2 from an age at exposure of 5 years to an age at exposure of 15 years (for a time since exposure of 12 years) and a decrease of the ERR from a time since exposure of 4 years to a time since exposure of 14 years of about 0.25 (for an age at exposure of 10 years). Central ERR estimates (of about 20 at 1 Gy for an age at exposure of 10 years and an attained age of 20 years) and their ratios for females compared to males (about 0.3) turn out to be relatively independent of the modeling. Excess absolute risk estimates are also predicted to be very similar from the different models. Risk models with parametric and categorical baselines were also applied to thyroid cancer incidence among the atomic bomb survivors. For young ages at exposure, the ERR values in the model with a parametric baseline are larger. Both data sets cover the period of 12 to 15 years since exposure. For this period, higher ERR values and a stronger age-at-exposure modification are found for the Chernobyl data set. Based on the results of the study, it is recommended to test parametric and categorical baseline models in risk analyses.
AU  - Walsh, L.*
AU  - Jacob, P.
AU  - Kaiser, J.C.
C1  - 775
C2  - 26471
CY  - United States
SP  - 509--518
TI  - Radiation risk modeling of thyroid cancer with special emphasis on the Chernobyl epidemiological data.
JO  - Radiat. Res.
VL  - 174
IS  - 4
PB  - Radiation Research Society
PY  - 2009
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Monte Carlo computer models that simulate the detailed, event-by-event transport of electrons in liquid water are valuable for the interpretation and understanding of findings in radiation chemistry and radiation biology. Because of the paucity of experimental data, such efforts must rely on theoretical principles and considerable judgment in their development. Experimental verification of numerical input is possible to only a limited extent. Indirect support for model validity can be gained from a comparison of details between two independently developed computer codes as well as the observable results calculated with them. In this study, we compare the transport properties of electrons in liquid water using two such models, PARTRAC and NOREC. Both use interaction cross sections based on plane-wave Born approximations and a numerical parameterization of the complex dielectric response function for the liquid. The models are described and compared, and their similarities and differences are highlighted. Recent developments in the field are discussed and taken into account. The calculated stopping powers, W values, and slab penetration characteristics are in good agreement with one another and with other independent sources.
AU  - Dingfelder, M.*
AU  - Ritchie, R.H.*
AU  - Turner, J.E.*
AU  - Friedland, W.
AU  - Paretzke, H.G.
AU  - Hamm, R.N.*
C1  - 2324
C2  - 25478
SP  - 584-594
TI  - Comparisons of calculations with PARTRAC and NOREC: Transport of electrons in liquid water.
JO  - Radiat. Res.
VL  - 169
IS  - 5
PB  - Radiation Research Society
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - In this study the solid cancer mortality data in the Techa River Cohort in the Southern Urals region of Russia was analyzed. The cohort received protracted exposure in the 1950s due to the releases of radioactive materials from the Mayak plutonium complex. The Extended Techa River Cohort includes 29,849 people who resided along the Techa River between 1950 and 1960 and were followed from January 1, 1950 through December 31, 1999. The analysis was done within the framework of the biologically based two-stage clonal expansion (TSCE) model. It was found that about 2.6% of the 1854 solid cancer deaths (excluding 18 bone cancer cases) could be related to radiation exposure. At age 63, which is the mean age for solid cancer deaths, the excess relative risk (ERR) and excess absolute risk (EAR) were found to be 0.76 Gy(-1) (95% CI 0.23; 1.29) and 33.0 (10(4) PY Gy)(-1) (95% CI 9.8; 52.6), respectively. These risk estimates are consistent with earlier excess relative risk analyses for the same cohort. The change in the ERR with age was investigated in detail, and an increase in risk with attained age was observed. Furthermore, the data were tested for possible signs of genomic instability, and it was found that the data could be described equally well by a model incorporating effects of genomic instability. Results from the TSCE models indicated that radiation received at older ages might have stronger biological effects than exposure at younger ages.
AU  - Eidemüller, M.
AU  - Ostroumova, E.*
AU  - Krestinina, L.*
AU  - Akleyev, A.*
AU  - Jacob, P.
C1  - 4030
C2  - 25140
SP  - 138-148
TI  - Analysis of solid cancer mortality in the Techa River cohort using the two-step clonal expansion model.
JO  - Radiat. Res.
VL  - 169
IS  - 2
PB  - Radiation Research Society
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Cells on the way to carcinogenesis can have a growth advantage relative to normal cells. It has been hypothesized that a radiation-induced growth advantage of these initiated cells might be induced by an increased cell replacement probability of initiated cells after inactivation of neighboring cells by radiation. Here Monte Carlo simulations extend this hypothesis for larger clones: The effective clonal expansion rate decreases with clone size. This effect is stronger for the two-dimensional than for the three-dimensional situation. The clones are irregular, far from a circular shape. An exposure-rate dependence of the effective clonal expansion rate could come in part from a minimal recovery time of the initiated cells for symmetric cell division.
AU  - Heidenreich, W.F.
AU  - Paretzke, H.G.
C1  - 3646
C2  - 25750
SP  - 613-617
TI  - Promotion of initiated cells by radiation-induced cell inactivation.
JO  - Radiat. Res.
VL  - 170
IS  - 5
PB  - Radiation Research Society
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Heidenreich, W.F.
AU  - Cullings, H.M.
AU  - Funamoto, S.
AU  - Paretzke, H.G.
C1  - 5847
C2  - 26124
SP  - 602-604
TI  - Criteria for Testing Promoting Action of Radiation in the Atomic Bomb Survivors Data.
JO  - Radiat. Res.
VL  - 169
IS  - 5
PB  - Radiation Research Society
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Jacob, P.
C1  - 4203
C2  - 25239
SP  - 602
TI  - Promoting action of radiation in the atomic bomb survivor cancer incidence data.
JO  - Radiat. Res.
VL  - 169
IS  - 5
PB  - Radiation Research Society
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Little, M. P., Tawn, E. J., Tzoulaki, I., Wakeford, R., Hildebrandt, G., Paris, F., Tapio, S. and Elliott, P. A Systematic Review of Epidemiological Associations Between Low and Moderate Doses of Ionizing Radiation and Late Cardiovascular Effects, and Their Possible Mechanisms. Radiat. Res. 169, 99-109 (2008). The link between high doses of ionizing radiation and damage to the heart and coronary arteries is established. In this paper, we systematically review the epidemiological evidence for associations between low and moderate doses (<5 Gy) of ionizing radiation and late-occurring cardiovascular disease. Risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding factors. An examination of possible biological mechanisms indicates that the most likely causative effect of radiation exposure is damage to endothelial cells and subsequent induction of an inflammatory response, although it seems unlikely that this would extend to low-dose and low-dose-rate exposure. However, a role for somatic mutation has been proposed that would indicate a stochastic effect. In the absence of a convincing mechanistic explanation of epidemiological evidence that is less than persuasive at present, a cause-and-effect interpretation of the reported statistical associations cannot be reliably inferred, although neither can it be reliably excluded. Further epidemiological and biological evidence will allow a firmer conclusion to be drawn.
AU  - Little, M.P.*
AU  - Tawn, E.J.*
AU  - Tzoulaki, I.*
AU  - Wakeford, R.*
AU  - Hildebrandt, G.*
AU  - Paris, F.*
AU  - Tapio, S.
AU  - Elliott, P.*
C1  - 1219
C2  - 26363
SP  - 99-109
TI  - A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms.
JO  - Radiat. Res.
VL  - 169
IS  - 1
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The case for a DNA-damaging action produced by radiofrequency (RF) signals remains controversial despite extensive research. With the advent of the Universal Mobile Telecommunication System (UMTS) the number of RF-radiation-exposed individuals is likely to escalate. Since the epigenetic effects of RF radiation are poorly understood and since the potential modifications of repair efficiency after exposure to known cytotoxic agents such as ionizing radiation have been investigated infrequently thus far, we studied the influence of UMTS exposure on the yield of chromosome aberrations induced by X rays. Human peripheral blood lymphocytes were exposed in vitro to a UMTS signal (frequency carrier of 1.95 GHz) for 24 h at 0.5 and 2.0 W/kg specific absorption rate (SAR) using a previously characterized waveguide system. The frequency of chromosome aberrations was measured on metaphase spreads from cells given 4 Gy of X rays immediately before RF radiation or sham exposures by fluorescence in situ hybridization. Unirradiated controls were RF-radiation- or sham-exposed. No significant variations due to the UMTS exposure were found in the fraction of aberrant cells. However, the frequency of exchanges per cell was affected by the SAR, showing a small but statistically significant increase of 0.11 exchange per cell compared to 0 W/kg SAR. We conclude that, although the 1.95 GHz signal (UMTS modulated) does not exacerbate the yield of aberrant cells caused by ionizing radiation, the overall burden of X-ray-induced chromosomal damage per cell in first-mitosis lymphocytes may be enhanced at 2.0 W/kg SAR. Hence the SAR may either influence the repair of X-ray-induced DNA breaks or alter the cell death pathways of the damage response.
AU  - Manti, L.*
AU  - Braselmann, H.
AU  - Calabrese, M.L.*
AU  - Massa, R.*
AU  - Pugliese, M.*
AU  - Scampoli, P.*
AU  - Sicignano, G.*
AU  - Grossi, G.*
C1  - 781
C2  - 25409
SP  - 575-583
TI  - Effects of modulated microwave radiation at cellular telephone frequency (1.95 GHz) on X-Ray-induced chromosome aberrations in human lymphocytes in vitro.
JO  - Radiat. Res.
VL  - 169
IS  - 5
PB  - Radiation Research Society
PY  - 2008
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Currently, EPR measurements are based on the assumption that odontogenesis (the series of events between the bud formation stage until the complete maturation of the tooth) is finished as soon as the tooth erupts. Consequently, it is also assumed that the hydroxyapatite concentration of the enamel (source of free radicals) does not depend on tooth age. However, the present work provides evidence that odontogenesis does not end after tooth eruption but continues for several years after eruption. Fifty-nine molars and pre-molars were analyzed by EPR spectroscopy. Tooth enamel samples were irradiated with different doses of ? radiation from a 60Co source. The resulting EPR signals were evaluated in terms of posteruption tooth age and tooth position. It was found that, except for wisdom teeth, the concentration of the dosimetric EPR free radicals increased with tooth age after eruption and became constant after a certain period. A mathematical equation was developed to describe this effect as a function of tooth age, tooth position and applied dose. The results suggest that EPR measurements obtained on young teeth should be interpreted carefully unless data are available that would allow one to describe the effect of posteruptive enamel maturation on the EPR estimated dose quantitatively. Little or no correction is needed for older teeth. Since only a limited number of young teeth were available for the present study, further studies are needed to clarify the situation and quantify this effect.
AU  - El-Faramawy, N.A.
AU  - Rühm, W.
C1  - 4882
C2  - 24389
SP  - 244-250
TI  - Additional Criteria for EPR Dosimetry using Tooth Enamel.
JO  - Radiat. Res.
VL  - 167
IS  - 2
PB  - Radiation Research Society
PY  - 2007
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Promoting Action of Radiation in the Atomic Bomb Survivor Carcinogenesis Data? Radiat. Res. 168, 750- 756 (2007).The age-time patterns of risk in the atomic bomb survivor data on incidence of solid cancers suggest an action of low-LET radiation not only on the initiating event but also on promotion in a biologically motivated model that allows for both actions. The favored model indicates a decrease of radiation risks with age at exposure due to the initiating effect and with time since exposure due to the promoting effect. These result in a relative risk that depends mostly on attained age for ages at exposure above 20 years. According to the model, a dose of 100 mGy is inducing about the same number of initiating events that occur spontaneously in 1 year. Assuming that several mutations are needed to obtain intermediate cells with growth advantage does not improve the quality of fit. The estimated promoting effect could be explained if the number of intermediate cells increases by 80% at 1 Gy, e.g. due to stimulated cell repopulation.
AU  - Heidenreich, W.F.
AU  - Cullings, H.M.*
AU  - Funamoto, S.*
AU  - Paretzke, H.G.
C1  - 4232
C2  - 24951
SP  - 750-756
TI  - Promoting action of radiation in the atomic bomb survivor carcinogenesis data?
JO  - Radiat. Res.
VL  - 168
IS  - 6
PB  - Radiation Research Soc.
PY  - 2007
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We investigated selected gene targets to differentiate radiation-induced papillary thyroid cancers (PTCs) from other etiologies. Total RNA was isolated from 11 post-Chernobyl PTCs and 41 sporadic PTCs characterized by a more aggressive tumor type and lacking a radiation exposure history. RNA from 10 tumor samples from both groups was pooled and hybridized separately on a whole genome microarray for screening. Then 92 selected gene targets were examined quantitatively on each tumor sample using an RTQ-PCR-based low-density array (LDA). Screening for more than fivefold differences in gene expression between the groups by microarray detected 646 up-regulated and 677 down-regulated genes. Categorization of these genes revealed a significant (P < 0.0006) over-representation of the number of up-regulated genes coding for oxidoreductases, G-proteins and growth factors, while the number of genes coding for immunoglobulin appeared to be significantly down-regulated. With the LDA, seven genes (SFRP1, MMP1, ESM1, KRTAP2-1, COL13A1, BAALC and PAGE1) made a complete differentiation between the groups possible. Gene expression patterns known to be associated with a more aggressive tumor type in older patients appeared to be more pronounced in post-Chernobyl PTC, thus underlining the known aggressiveness of radiation-induced PTC. Seven genes were found that completely distinguished post-Chernobyl (PTC) from sporadic PTC.
AU  - Port, M.*
AU  - Boltze, C.*
AU  - Wang, Y.
AU  - Röper, B.*
AU  - Meineke, V.*
AU  - Abend, M.*
C1  - 1369
C2  - 25519
SP  - 639-649
TI  - A radiation-induced gene signature distinguishes post-Chernobyl from sporadic papillary thyroid cancers.
JO  - Radiat. Res.
VL  - 168
IS  - 6
PB  - Radiation Research Society
PY  - 2007
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Radiation exposure leads to a risk for long-term deterministic and stochastic late effects. Two individuals exposed to protracted photon radiation in the radiological accident at the Lilo Military site in Georgia in 1997 received follow-up treatment and resection of several chronic radiation ulcers in the Bundeswehr Hospital Ulm, Germany, in 2003. Multi-parameter analysis revealed that spermatogenetic arrest and serum hormone levels in both patients had recovered compared to the status in 1997. However, we observed a persistence of altered T-cell ratios, increased ICAM1 and beta1-integrin expression, and aberrant bone marrow cells and lymphocytes with significantly increased translocations 6 years after the accident. This investigation thus identified altered end points still detectable years after the accident that suggest persistent genomic damage as well as epigenetic effects in these individuals, which may be associated with an elevated risk for the development of further late effects. Our observations further suggest the development of a chronic radiation syndrome and indicate follow-up parameters in radiation victims.
AU  - Scherthan, H.*
AU  - Abend, M.*
AU  - Müller, K.*
AU  - Beinke, C.*
AU  - Braselmann, H.
AU  - Zitzelsberger, H.
AU  - Köhn, F.M.*
AU  - Pillekamp, H.*
AU  - Schiener, R.*
AU  - Das, O.*
AU  - Peter, R.U.*
AU  - Herzog, G.*
AU  - Tzschach, A.*
AU  - Dörr, H.D.*
AU  - Fliedner, T.M.*
AU  - Meineke, V.*
C1  - 4523
C2  - 24957
SP  - 615-623
TI  - Radiation-induced late effects in two affected individuals of the Lilo radiation accident.
JO  - Radiat. Res.
VL  - 167
IS  - 5
PB  - Radiation Research Soc.
PY  - 2007
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Heidenreich, W.F.
AU  - Carnes, B.A.*
AU  - Paretzke, H.G.
C1  - 2912
C2  - 24094
SP  - 794-801
TI  - Lung cancer risk in mice: Analysis of fractionation effects and neutron RBE with a biologically motivated model.
JO  - Radiat. Res.
VL  - 166
PY  - 2006
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Jacob, P.
AU  - Bogdanova, T.I.*
AU  - Buglova, E.*
AU  - Chepurniy, M.*
AU  - Demidchik, Y.*
AU  - Gavrilin, Y.*
AU  - Kenigsberg, J.*
AU  - Meckbach, R.
AU  - Schotola, C.
AU  - Shinkarev, S.*
AU  - Tronko, M.D.*
AU  - Ulanowski, A.
AU  - Vavilov, S.*
AU  - Walsh, L.
C1  - 3371
C2  - 23482
SP  - 1-8
TI  - Thyroid cancer risk in areas of Ukraine and Belarus affected by the Chernobyl accident.
JO  - Radiat. Res.
VL  - 165
PY  - 2006
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Tschiersch, J.
AU  - Haninger, T.
C1  - 151
C2  - 23727
SP  - 120-121
TI  - Adjusting lung cancer risks for temporal and spatial variations in radon concentrations in Dwellings in Gansu Province, China.
JO  - Radiat. Res.
VL  - 166
PY  - 2006
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Atkinson, M.J.
AU  - Spanner, M.T.
AU  - Rosemann, M.
AU  - Linzner, U.
AU  - Müller, W.A.
AU  - Gössner, W.
C1  - 3023
C2  - 22836
SP  - 230-233
TI  - Intracellular sequestration of 223Ra by the iron-storage protein ferritin.
JO  - Radiat. Res.
VL  - 164
PY  - 2005
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Gomolka, M.*
AU  - Rössler, U.*
AU  - Hornhardt, S.*
AU  - Walsh, L.*
AU  - Panzer, W.
AU  - Schmid, E.
C1  - 2629
C2  - 22648
SP  - 510-519
TI  - Measurement of the initial levels of DNA damage in human lymphocytes induced by 29 kV X rays (Mammography X rays) relative to 220 kV X rays and gamma rays.
JO  - Radiat. Res.
VL  - 163
PY  - 2005
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Likhtarov, I.*
AU  - Kovgan, L.*
AU  - Vavilov, S.*
AU  - Chepurny, M.*
AU  - Bouville, A.*
AU  - Luckyanov, N.*
AU  - Jacob, P.
AU  - Voillequé, P.*
AU  - Voigt, G.*
C1  - 2187
C2  - 22472
SP  - 125-136
TI  - Post-Chernobyl thyroid cancers in Ukraine. Report 1: Estimation of thyroid doses.
JO  - Radiat. Res.
VL  - 163
PY  - 2005
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Shishkina, E.A.*
AU  - Göksu, H.Y.
AU  - El-Faramawy, N.A.
AU  - Semioshkina, N.A.
C1  - 1600
C2  - 22587
SP  - 462-467
TI  - Assessment of 90Sr concentration in dental tissue using thin-layer beta-particle detectors and verification with numerical calculations.
JO  - Radiat. Res.
VL  - 163
PY  - 2005
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - no abstract
AU  - Heidenreich, W.F.
AU  - Luebeck, E.G.*
AU  - Hazelton, W.D.*
AU  - Paretzke, H.G.
AU  - Moolgavkar, S.H.*
C1  - 3062
C2  - 21716
SP  - 369-371
TI  - Response to the Commentary of Donald A. Pierce (Radiat. Res. 160, 718-723, 2003)
JO  - Radiat. Res.
VL  - 161
IS  - 3
PY  - 2004
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The simulations in this paper show that exposure measurement error affects the parameter estimates of the biologically motivated two-stage clonal expansion (TSCE) model. For both Berkson and classical error models, we show that likelihood-based techniques of correction work reliably. For classical errors, the distribution of true exposures needs to be known or estimated in addition to the distribution of recorded exposures conditional on true exposures. Usually the exposure uncertainty biases the model parameters toward the null and underestimates the precision. But when several parameters are allowed to be dependent on exposure, e.g. initiation and promotion, then their relative importance is also influenced, and more complicated effects of exposure uncertainty can occur. The application part of this paper shows for two different types of Berkson errors that a recent analysis of the data for the Colorado plateau miners with the TSCE model is not changed substantially when correcting for such errors. Specifically, the conjectured promoting action of radon remains as the dominant radiation effect for explaining these data. The estimated promoting action of radon increases by a factor of up to 1.2 for the largest assumed exposure uncertainties.
AU  - Heidenreich, W.F.
AU  - Luebeck, E.G.*
AU  - Moolgavkar, S.H.*
C1  - 3720
C2  - 21475
SP  - 72-81
TI  - Effects of exposure uncertainties in the TSCE model and application to the Colorado miners data.
JO  - Radiat. Res.
VL  - 161
IS  - 1
PB  - Radiation Research Society
PY  - 2004
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Bergner, A.*
AU  - Stief, J.*
AU  - Holdenrieder, S.*
AU  - Stieber, P.*
AU  - Haimerl, W.*
AU  - Passlick, B.*
AU  - Waldschmidt, A.
AU  - Kummermehr, J.C.
AU  - Gamarra, F.*
AU  - Huber, R.M.*
C1  - 9510
C2  - 21435
SP  - 647-654
TI  - Effects of Single-Dose Irradiation on Bronchial Epithelium : A Comparison of BEAS 2B Cell Monolayers, Human Organ Cultures and Goettinger Minipigs.
JO  - Radiat. Res.
VL  - 160
PY  - 2003
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Friedland, W.
AU  - Jacob, P.
AU  - Bernhardt, P.
AU  - Paretzke, H.G.
AU  - Dingfelder, M.
C1  - 9879
C2  - 20897
SP  - 401-410
TI  - Simulation of DNA Damage after Proton Irradiation.
JO  - Radiat. Res.
VL  - 159
PY  - 2003
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Heidenreich, W.F.
AU  - Nyberg, U.*
AU  - Hall, P.*
C1  - 9880
C2  - 21058
SP  - 656-662
TI  - A Biologically Based Model for Liver Cancer Risk in the Swedish Thorotrast Patients.
JO  - Radiat. Res.
VL  - 159
PY  - 2003
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Kellerer, A.M.
AU  - Chen, J.*
C1  - 9511
C2  - 21452
SP  - 324-333
TI  - Comparative microdosimetry of photoelectrons and compton electrons : An analysis in terms of generalized proximity functions.
JO  - Radiat. Res.
VL  - 160
PY  - 2003
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Schmid, E.
AU  - Krumrey, M.*
AU  - Ulm, G.*
AU  - Roos, H.*
AU  - Regulla, D.F.
C1  - 9881
C2  - 21300
SP  - 499-504
TI  - The Maximum Low-Dose RBE of 17.4 and 40 keV Monochromatic X Rays for the Induction of Dicentric Chromosomes in Human Peripheral Lymphocytes.
JO  - Radiat. Res.
VL  - 160
PY  - 2003
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Kellerer, A.M.
C1  - 9515
C2  - 20580
SP  - 13-22
TI  - Electron spectra and the RBE of X rays.
JO  - Radiat. Res.
VL  - 158
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Kellerer, A.M.
AU  - Walsh, L.*
C1  - 9516
C2  - 20584
SP  - 61-68
TI  - Solid cancer risk coefficient for fast neutrons in terms of effective dose.
JO  - Radiat. Res.
VL  - 158
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The low-energy secondary electrons emerging from the entrance surface of an X-irradiated gold foil increase the dose to cells in contact with or at micrometer distances from this surface (Radiat. Res. 150, 92-100, 1998). We examined the effect of the spectrum of these low-energy electrons on the RBE for cytogenetic effects and showed that this RBE was increased. A monolayer of surface-attached human T lymphocytes was exposed to 60 kV X rays in the absence or presence of a gold foil positioned immediately behind the cell layer or separated from it by a Mylar foil 0.9 or 2 mum thick. The enhancement of dose in the cell nuclei caused by the photoelectrons and Auger electrons emerging from the entrance surface of the gold foil was measured by TSEE dosimetry. Dose enhancement factors of 55.7, 46.6 and 37.5 were obtained with 0, 0.9 and 2 mum of Mylar inserted between the gold surface and the cell layer. This large enhancement results from the photoelectric effect in the gold foil, as shown by the accompanying Monte Carlo calculations of the secondary electron spectra at the gold surface. Auger electrons from the gold foil generally were not able to penetrate into the cell nuclei except for that fraction of the cells that had a very thin (< 0.7 mum) layer of cytoplasm and membranes between gold surface and cell nucleus. The dose-yield curves for dicentric chromosomes plus centric rings and for acentric fragments obtained after exposures without or with the gold foil were linear-quadratic. The coefficient alpha, the slope of the linear yield component, was increased in the presence of the gold foil and showed RBE values ranging from 1.7 to 2.2 compared to exposures in absence of the gold foil. The ratio of the yield of interstitial deletions and dicentrics (H ratio) was significantly increased from about 0.17 in the absence of the gold foil to about 0.22 in the presence of the gold foil. The increases in the RBE and the H ratio are interpreted in microdosimetric terms: The preferred occurrence of electron track ends in the vicinity of the gold surface causes an increase in the dose-mean restricted linear energy transfer in cell nuclei exposed to the photoelectrons and Auger electrons.
AU  - Regulla, D.F.
AU  - Schmid, E.
AU  - Friedland, W.
AU  - Panzer, W.
AU  - Heinzmann, U.
AU  - Harder, D.*
C1  - 9513
C2  - 20331
SP  - 505-515
TI  - Enhanced Values of the RBE and H Ratio for Cytogenetic Effects Induced by Secondary Electrons from an X-Irradiated Gold Surface.
JO  - Radiat. Res.
VL  - 158
PB  - Society
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The present study was carried out to determine the extent to which genetic factors modify the incidence of radiation-induced bone tumorigenesis in mice, and to map putative susceptibility genes. We conducted a genome-wide linkage analysis in a cohort of 47 interstrain backcrossed mice. After the mice were injected with the bone-seeking alpha-particle-emitting radionuclide Th-227, 21 of the mice developed osteosarcomas. Two loci, one on chromosome 7 close to D7Mit145 and a second on chromosome 14 (D14Mit125), exhibited suggestive linkage to osteosarcoma predisposition, with LOD scores of 1.37 and 1.05, respectively. The LOD score increased considerably when interaction between these two loci was taken into account (LOD = 3.48). Nine of 12 mice inheriting a susceptibility allele at both loci developed osteosarcomas after 227Th injection, compared to only four osteosarcomas in 18 animals that did not inherit either of the susceptibility alleles. Variance component analysis revealed that these genetic factors determine approximately one-fifth of the total incidence of osteosarcomas. This study demonstrates the presence of a genetic component that modulates predisposition to radiation-induced osteosarcoma.
AU  - Rosemann, M.
AU  - Lintrop, M.
AU  - Favor, J.
AU  - Atkinson, M.J.
C1  - 9514
C2  - 20448
SP  - 426-434
TI  - Bone tumorigenesis induced by alpha-particle radiation: Mapping of genetic loci influencing predisposition in mice.
JO  - Radiat. Res.
VL  - 157
PB  - Radiation Research Society
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The RBE for neutrons was assessed in a head-to-head experiment in which cultures of lymphocytes from the same male donor were irradiated simultaneously with 144 keV neutrons and with Co-60 gamma rays as the reference radiation and evaluated using matched time, culture conditions, and the end point of chromosomal aberrations to avoid potential confounding factors that would influence the outcome of the experiment. In addition, the irradiation time was held constant at 2 h for the high-dose groups for both radiation types, which resulted in rather low dose rates. For the induction of dicentric chromosomes, the exposure to the 144 keV neutrons was found to be almost equally as effective (yield coefficient alpha(dic) = 0.786 +/- 0.066 dicentrics per cell per gray) as that found previously for irradiation with monoenergetic neutrons at 565 keV (alpha(dic) = 0.813 +/- 0.052 dicentrics per cell per gray) under comparable exposure and culture conditions (Radiat. Res. 154, 307-312, 2000). However, the values of the maximum low-dose RBE (RBEm) relative to (CO)-C-60 gamma rays that were determined in the present and previous studies show an insignificant but conspicuous difference: 57.0 +/- 18.8 and 76.0 +/- 29.5, respectively. This difference is mainly due to the difference in the alpha(dic) value of the (CO)-C-60 gamma rays, the reference radiation, which was 0.0138 +/- 0.0044 Gy(-1) in the present study and 0.0107 +/- 0.0041 Gy(-1) in the previous study. In the present experiment, irradiations with 144 keV neutrons and (CO)-C-60 gamma rays were both performed at 21degreesC, while in the earlier experiment irradiations with 565 keV neutrons were performed at 21degreesC and the corresponding reference irradiation with gamma rays was performed at 37degreesC. However, the temperature difference between 21degreesC and 37degreesC has a minor influence on the yield of chromosomal alterations and hence RBE values. The large cubic PMMA phantom that was used for the gamma irradiations in the present study results in a larger dose contribution from Compton-scattered photons compared to the mini-phantom used in the earlier experiments. The contribution of these scattered photons may explain the large value of alpha(dic) for gamma irradiation in the present study. These results indicate that the yield coefficient alpha(dic) for 144 keV neutrons is similar to the one for 565 keV neutrons, and that modification of the alpha(dic) value of the low-LET reference radiation, due to changes in the experimental conditions, can influence the RBEm. Consequently, alpha(dic) values cannot be shared between cytogenetic laboratories for the purpose of assessment of RBMm without verification of the comparability of the experimental conditions.
AU  - Schmid, E.
AU  - Regulla, D.F.
AU  - Guldbakke, S.*
AU  - Schlegel, D.*
AU  - Roos, M.
C1  - 9512
C2  - 20182
SP  - 453-460
TI  - Relative Biological Effectiveness of 144 keV Neutrons in Producing Dicentric Chromosomes in Human Lymphocytes Compared with 60Co Gamma Rays under Head-to-Head Conditions.
JO  - Radiat. Res.
VL  - 157
PB  - Society
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Schmid, E.
AU  - Regulla, D.F.
AU  - Kramer, H.-M.*
AU  - Harder, D.*
C1  - 9517
C2  - 20646
SP  - 771-777
TI  - The Effect of 29 kV X Rays on the Dose Response of Chromosome Aberrations in Human Lymphocytes.
JO  - Radiat. Res.
VL  - 158
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Schmid, E.
C1  - 9518
C2  - 21064
SP  - 778-781
TI  - Is There Reliable Experimental Evidence for a Low-Dose RBE of about 4 for Mammography X Rays Relative to 200 kV X Rays?
JO  - Radiat. Res.
VL  - 158
PY  - 2002
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Friedland, W.
AU  - Li, W.B.
AU  - Jacob, P.
AU  - Paretzke, H.G.
C1  - 21738
C2  - 19928
SP  - 703-715
TI  - Simulation of Exon Deletion Mutations Induced by LOW-LET Radiation at the HPRT Locus.
JO  - Radiat. Res.
VL  - 155
PY  - 2001
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Heidenreich, W.F.
AU  - Paretzke, H.G.
C1  - 21747
C2  - 19943
SP  - 678-681
TI  - The Two-Stage Clonal Expansion Model as an Example of a Biologically Based Model of Radiation- Induced Cancer.
JO  - Radiat. Res.
VL  - 156
PY  - 2001
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Li, W.B.
AU  - Friedland, W.
AU  - Pomplun, E.*
AU  - Jacob, P.
AU  - Paretzke, H.G.
AU  - Lassmann, M.*
AU  - Reiners, Ch.*
C1  - 9519
C2  - 21830
SP  - 419-429
TI  - Track structures and dose distributions from decays of 131I and 125I in and around water spheres simulating micrometastases of differentiated thyroid cancer.
JO  - Radiat. Res.
VL  - 156
PY  - 2001
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Regulla, D.F.
AU  - Panzer, W.
AU  - Schmid, E.
AU  - Stephan, G.*
AU  - Harder, D.*
C1  - 21732
C2  - 19934
SP  - 744-747
TI  - Detection of Elevated RBE in Human Lymphocytes Exposed to Secondary Electrons Released from X-Irradiated Metal Surfaces.
JO  - Radiat. Res.
VL  - 155
PY  - 2001
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Neoplastic transformation of human epithelial cells by radiation has previously been investigated using cell lines immortalized with viral vectors. There are disadvantages to this approach, and we report here the results of studies using a human retinal pigment epithelial cell line (340RPE-T53) immortalized by treatment with telomerase. After exposure of the cells to fractionated doses of gamma radiation, there was a marked increase in anchorage-independent growth of the surviving cells. The cloned cell lines derived from these anchorage-independent cultures exhibited an increased growth rate in vitro and were serum-independent compared with the parent cell line. The parent cell line maintained a stable diploid karyotype, The cell lines cloned after irradiation with the lower doses (10 x 2 Gy) were hypodiploid with loss of chromosome 13 and a high level amplification of 10p11.2 associated with a deletion of the remaining short arm segment of chromosome 10 distal to 10p11.2. In contrast, the cell lines cloned after irradiation with the higher doses (15 x 2 Gy) were neartetraploid with derivative chromosomes present characterized by SKY analysis. Thus this human epithelial cell line immortalized with telomerase provides an improved model to investigate mechanisms of radiation carcinogenesis.
AU  - Riches, A.*
AU  - Peddie, C.*
AU  - Rendell, S.*
AU  - Bryant, P.*
AU  - Zitzelsberger, H.
AU  - Bruch, J.
AU  - Smida, J.
AU  - Hieber, L.
AU  - Bauchinger, M.
C1  - 23344
C2  - 31099
SP  - 222-229
TI  - Neoplastic transformation and cytogenetic changes after gamma irradiation of human epithelial cells expressing telomerase.
JO  - Radiat. Res.
VL  - 155
IS  - 1
PB  - Radiation Research Society
PY  - 2001
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Zankl, M.
C1  - 9878
C2  - 19343
SP  - 192-194
TI  - Mathematical Phantoms. 
JO  - Radiat. Res.
VL  - 2
PB  - Society
PY  - 2000
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Heidenreich, W.F.
AU  - Kenigsberg, J.*
AU  - Jacob, P.
AU  - Buglova, E.*
AU  - Goulko, G.
AU  - Paretzke, H.G.
AU  - Demidchik, E.P.*
AU  - Golovneva, A.*
C1  - 20874
C2  - 18931
SP  - 617-625
TI  - Time trends of thyroid cancer incidence in belarus after the Chernobyl accident.
JO  - Radiat. Res.
VL  - 151
PY  - 1999
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Heidenreich, W.F.
AU  - Jacob, P.
AU  - Paretzke, H.G.
AU  - Gross, F.T.*
AU  - Dagle, G.E.*
C1  - 20984
C2  - 19035
SP  - 209-217
TI  - Two-step for the risk of fatal and incidental lung tumors in rats exposed to radon.
JO  - Radiat. Res.
VL  - 151
PY  - 1999
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Kreuzer, M.*
AU  - Grosche, B.*
AU  - Brachner, A.*
AU  - Martignoni, K.*
AU  - Schnelzer,M.*
AU  - Schopka, H.-J.*
AU  - Brüske, I.
AU  - Wichmann, H.-E.
AU  - Burkart, W.*
C1  - 21081
C2  - 19114
SP  - 56-58
TI  - The German uranium miners cohort study: Feasibility and First Results.
JO  - Radiat. Res.
VL  - 152
PY  - 1999
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Luebeck, E.G.*
AU  - Heidenreich, W.F.
AU  - Hazelton, W.D.*
AU  - Paretzke, H.G.
AU  - Moolgavkar, S.H.*
C1  - 21067
C2  - 19097
SP  - 339-351
TI  - Biologically Based Analysis of the Data for the Colorado Uranium Miners Cohort: Age, Dose and Dosse-Rate Effects.
JO  - Radiat. Res.
VL  - 152
PY  - 1999
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Saran, M.
AU  - Hamm, U.
AU  - Friedl, A.A.
AU  - Bors, W.
C1  - 20758
C2  - 17390
SP  - 232-235
TI  - Radiation-induced cell killing is highly dependent upon buffer treatment (filtration compared to autoclaving) due to metal-catalyzed formation of hypochlorite: a cautionary note.
JO  - Radiat. Res.
VL  - 146
PY  - 1996
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Bone sarcomas may be induced throughout the skeleton (systemic) in mice by relatively low internal alpha-particle doses that are distributed over the whole skeleton. The induction of local (periosteal) bone sarcomas after paratibial deposition of insoluble radiocolloids required much higher doses, and in addition high energies of emitted particles. Paratibial deposition of alpha-particle-emitting radiocolloids of 227Th and 228Th resulted in formation of both local and systemic bone sarcomas. The latter were most probably induced by the released radium daughters of the thorium isotopes and were distributed about the skeleton. Paratibial injections with beta-particle emitters 144Ce+ 144Pr (29 kBq per mouse) showed an incidence of local bone sarcomas of more than 80%. An estimation of the local effective doses led to values of more than 1000 Gy for the beta-particle emitter 144Ce and around 150 Gy for the thorium isotopes. Thus induction of local bone sarcomas required doses considerably greater than those needed for systemic bone sarcomas. The local induction of bone sarcomas has been reported for high-energy beta particles using similar high doses of 144Ce+ 144Pr in rats and for external 90Sr+ 90Y irradiation in mice. We conclude that the processes involved in the induction of local and systemic bone sarcomas by radiation may be quite different.
AU  - Müller, W.A.
AU  - Luz, A.
AU  - Linzner, U.
C1  - 27604
C2  - 32762
SP  - 415-422
TI  - Radiation-induced systemic and local bone tumors: Two types of late effects with possible different origins?
JO  - Radiat. Res.
VL  - 138
IS  - 3
PB  - Radiation Res. Soc.
PY  - 1994
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Miller, R.C.
AU  - Randers-Pehrson, G.
AU  - Hieber, L.
AU  - Marino, S.A.
AU  - Richards, M.
AU  - Hall, E.J.
C1  - 20667
C2  - 13882
SP  - 360-364
TI  - The Inverse Dose-Rate Effect for Oncogenic Transformation by Charged Particles is Dependent on Linear Energy Transfer.
JO  - Radiat. Res.
VL  - 133
PY  - 1993
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Microdosimetric measurements in beams of diagnostic X rays (between 30 and 125 kV) have been performed. In these pulsed radiation fields, microdosimetric measurements are possible only by application of the variance-covariance technique. The dose mean lineal energy, ȳ(D), is determined for various simulated diameters, at different depths in the absorber, and at different points within the pulse intervals. From the measured temporal dependences one can also obtain values of ȳ(D) for different X-ray pulse generators. The results demonstrate the potential of the variance-covariance method for a diversity of microdosimetric measurements in radiation protection and in the quality control of radiation beams.
AU  - Chen, J.
AU  - Roos, H.
AU  - Kellerer, A.M.
C1  - 40542
C2  - 38018
SP  - 271-276
TI  - Microdosimetry of diagnostic X rays: Applications of the variance- covariance method.
JO  - Radiat. Res.
VL  - 132
IS  - 3
PY  - 1992
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Fluorescence in situ hybridization using simultaneously a combination of DNA probes for the telomeric hexamer repeat (TTAGGG) and the centromerically repeated murine γ-satellite DNA was applied to analyze the nature of radiation-induced micronuclei in mouse NIH 3T3 fibroblasts. After subtraction of spontaneously occurring micronuclei independent from the dose and time after irradiation, approximately 22% of the radiation-induced micronuclei did not reveal any hybridization signal. Approximately 17% showed one centromeric hybridization signal and about four telomeric signals, suggesting their origin from whole chromosomes. Almost 60% of radiation-induced micronuclei had telomeric signals only, suggesting their origin from acentric fragments. A fraction of micronuclei were found to contain two or more acentric fragments. Micronuclei derived from whole chromosomes or from multiple acentric fragments might, together with DNA synthesis in micronuclei, explain the occurrence of radiation-induced micronuclei with DNA contents greater than the largest chromosome arm.
AU  - Miller, B.M.
AU  - Werner, T.
AU  - Weier -, H.U.G.
AU  - Nüsse, M.
C1  - 40668
C2  - 12873
SP  - 177-185
TI  - Analysis of radiation-induced micronuclei by fluorescence in situ hybridization (FISH) simultaneously using telomeric and centromeric DNA probes.
JO  - Radiat. Res.
VL  - 131
IS  - 2
PY  - 1992
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - o study further the pathophysiology of radiation-induced cardiomyopathy, we investigated resting hemodynamics, myocardial catecholamine synthesis and storage, and beta-adrenoceptor density after local heart irradiation. In Wistar rats, a radiation dose of 20 Gy eventually leads to compromised myocardial function which is characterized by a reduction in cardiac output to 43 +/- 11% and in the left ventricular ejection fraction to 66 +/- 7.5%, and an increase in the left ventricular end-diastolic volume to 187 +/- 17% of control values. This reduction in function is correlated with focal degeneration of 23 +/- 4% of the myocardium. Measurement of tyrosine hydroxylase activity and catecholamine content revealed that catecholamine biosynthesis is unchanged in the adrenals but is significantly reduced in the hearts of irradiated animals, while cardiac beta-adrenoceptor density is increased to about 140% of that in age-matched controls. This is in contrast to findings in dilated or ischemic cardiomyopathy. Time-course studies showed that the development of myocardial degeneration starts simultaneously with the decrease in cardiac output and ejection fraction and the increase in beta-adrenoceptors at 50-80 days postirradiation. Myocardial degeneration is maximal in extent and severity at 100 days and does not progress thereafter. Cardiac output decreases at 80-100 days postirradiation to 60 +/- 7% of control values. A significant further decrease is seen only when congestive heart failure becomes manifest at 249 +/- 21 days after 20 Gy. Thus there is a delay between structural myocardial injury and hemodynamic deterioration which could be due to a compensatory increase in beta-adrenoceptor density during the initial stages of the cardiomyopathy.
AU  - Schultz-Hector, S.
AU  - Böhm, A.
AU  - Blöchel, A.
AU  - Dominiak, P.
AU  - Erdmann, E.
AU  - Müller-Schauenburg, W.
AU  - Weber, A.
C1  - 18756
C2  - 11869
SP  - 281-289
TI  - Radiation-induced heart disease: Morphology, changes in catecholamine synthesis and content, ß-adrenoceptor density and hemodynamic function in an experimental model.
JO  - Radiat. Res.
VL  - 129
IS  - 3
PY  - 1992
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - DNA double-strand breaks (DSBs) are 2.9 times more frequently induced in yeast cells exposed to sparsely ionizing 30-MeV electrons under oxic compared to anoxic conditions. The rejoining of DSBs induced under anoxic conditions was investigated under conditions allowing repair of potentially lethal damage and compared to the rejoining of DSBs induced in oxic cells. In contrast to the biphasic rejoining kinetics of DSBs induced in oxic cells, the rejoining kinetics of DSBs induced in anoxic cells is complicated by the formation of secondary DSBs. These arise during postirradiation incubation of cells, presumably as a consequence of repair processes acting on radiation-induced lesions other than DSBs. These secondary DSBs may at least partially explain the finding that a greater fraction of unrejoinable DSBs is present in cells irradiated under anoxic compared to oxic conditions. As a consequence, the oxygen enhancement ratio of the yield of the remaining DSBs is decreasing in the course of DSB rejoining.
AU  - Frankenberg-Schwager, M.
AU  - Frankenberg, D.
AU  - Harbich, R.
C1  - 18329
C2  - 11519
SP  - 243-250
TI  - Different Oxygen Enhancement Ratios for Induced and Unrejoined DNA Double-Strand Breaks in Eukaryotic Cells.
JO  - Radiat. Res.
VL  - 128
IS  - 3
PY  - 1991
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - DNA double-strand breaks (DSBs) are 2.9 times more frequently induced in yeast cells exposed to sparsely ionizing 30-MeV electrons under oxic compared to anoxic conditions. The rejoining of DSBs induced under anoxic conditions was investigated under conditions allowing repair of potentially lethal damage and compared to the rejoining of DSBs induced in oxic cells. In contrast to the biphasic rejoining kinetics of DSBs induced in oxic cells, the rejoining kinetics of DSBs induced in anoxic cells is complicated by the formation of secondary DSBs. These arise during postirradiation incubation of cells, presumably as a consequence of repair processes acting on radiation- induced lesions other than DSBs. These secondary DSBs may at least partially explain the finding that a greater fraction of unrejoinable DSBs is present in cells irradiated under anoxic compared to oxic conditions. As a consequence, the oxygen enhancement ratio of the yield of the remaining DSBs is decreasing in the course of DSB rejoining.
AU  - Frankenberg-Schwager, M.
AU  - Frankenberg, D.
AU  - Harbich, R.
C1  - 40795
C2  - 38042
SP  - 243-250
TI  - Different oxygen enhancement ratios for induced and unrejoined DNA double- strand breaks in eukaryotic cells.
JO  - Radiat. Res.
VL  - 128
IS  - 3
PY  - 1991
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Paretzke, H.G.
AU  - Turner, J.E.
AU  - Hamm, R.N.
AU  - Ritchie, R.H.
AU  - Wright, H.A.
C1  - 19901
C2  - 13055
SP  - 121-129
TI  - Spatial Distributions of Inelastic Events Produced by Electrons in Gaseous and Liquid Water.
JO  - Radiat. Res.
VL  - 127
PY  - 1991
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis. In an earlier analysis [H. Spiess and C.W. Mays, in Radiation Carcinogenesis. (C.L. Sanders et al., Eds). pp 437-450. USAEC Symposium Series 29, CONF-720505, 1973] it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas. The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients. In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods. A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test. In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose. A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment. The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18·τ), where τ is the treatment time in months. This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma.
AU  - Chmelevsky, D.
AU  - Spieß, H.F.
AU  - Mays, C.W.
AU  - Kellerer, A.M.
C1  - 41991
C2  - 40145
SP  - S69-S79
TI  - The reverse protraction factor in the induction of bone sarcomas in radium-224 patients.
JO  - Radiat. Res.
VL  - 124
IS  - 1 SUPPL.
PY  - 1990
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Kellerer, A.M.
AU  - Barclay, D.
C1  - 19259
C2  - 12330
TI  - Risk projections under two multiplicative models for cancer mortality among the atomic Bomb survivors.
JO  - Radiat. Res.
PY  - 1990
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The effect of injection of 1.85 kBq/kg of the long-lived radionuclide 227Ac on the induction of osteosarcomas in female NMRI mice by different dose levels (18.5, 74, and 185 kBq/kg) of the short-lived radionuclide 227Th was investigated. The highest absolute osteosarcoma incidence was observed with the highest doses of 227Th. Addition of 227Ac resulted in an additional osteosarcoma incidence only at the lowest dose of 227Th and did not affect the osteosarcoma incidence resulting from higher doses of 227Th. The longest times to tumor appearance were observed with 227Ac alone. The latent period in two different age groups (4 weeks and 10-12 weeks) appeared to be similar following injection with combined doses of 227Th and 227Ac but different after injection of each radionuclide alone.
AU  - Müller, W.A.
AU  - Murray, A.B.
AU  - Linzner, U.
AU  - Luz, A.
C1  - 42348
C2  - 11017
SP  - 14-20
TI  - Osteosarcoma risk after simultaneous incorporation of the long-lived radionuclide 227Ac and the short-lived radionuclide 227Th.
JO  - Radiat. Res.
VL  - 121
IS  - 1
PY  - 1990
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - van den Aardweg, G.J.M.J.
AU  - Arnold, M.
AU  - Hopewell, J.W.
C1  - 18195
C2  - 11405
SP  - 283-287
TI  - A Comparison of the Radiation Response of the Epidermis in Two Strains of Pig.
JO  - Radiat. Res.
VL  - 124
IS  - 3
PY  - 1990
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The effect of local X irradiation on cardiac α and β receptors was studied in Wistar rats. Animals were given local heart irradiation with single doses of 15 or 20 Gy and were examined after a range of latency times of 7 to 400 days. Using the radioactive ligands [3H]CGP-12177 and [3H]prazosin, the maximal binding capacity was determined from saturation experiments. At 7 days after 20 Gy the maximal binding capacity of both α and β receptors was reduced to below the level of untreated control animals. Subsequently it rose continually to a maximum of 160% of the control level for β receptors and 130% for α receptors at 400 days postirradiation. The antagonists affinity as judged from the dissociation constant for [3H]CGP-12177 and [3H]-prazosin did not change significantly. A similar effect was observed after 15 Gy. An increase in adrenergic receptors may represent an important pathogenetic link between early morphological and late functional changes in the pathogenesis of radiation-induced heart disease.
AU  - Lauk, S.
AU  - Böhm, M.P.
AU  - Feiler, G.
AU  - Geist, B.J.
AU  - Erdmann-, E.
C1  - 41815
C2  - 10584
SP  - 157-165
TI  - Increased number of cardiac adrenergic receptors following local heart irradiation.
JO  - Radiat. Res.
VL  - 119
IS  - 1
PY  - 1989
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Yeung, T.K.
AU  - Lauk, S.
AU  - Simmonds, R.H.
AU  - Hopewell, J.W.
AU  - Trott, K.-R.
C1  - 17886
C2  - 11206
SP  - 489-499
TI  - Morphological and Functional Changes in the Rat Heart after X Irradiation: Strain Differences.
JO  - Radiat. Res.
VL  - 119
PY  - 1989
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The incidence of lens opacifications that impaired vision (cataract) was analyzed among 831 patients who were injected with known dosages of 224Ra in Germany shortly after World War II. The dependence of the incidence on dosage, i.e., injected activity per unit body weight, and on time after treatment was determined. The observations are equally consistent with proportionality of the incidence of cataract to the square of dosage or with a linear dependence beyond a threshold of 0.5 MBq/kg. The possibility of a linear dependence without threshold was strongly rejected (P < 0.001). The analysis of temporal dependences yielded a component that was correlated with the injected amount of 224Ra and a component that was uncorrelated. The former was inferred by a maximum likelihood analysis to increase approximately as the square of the time after treatment. The component unrelated to the treatment was found to increase steeply with age and to become dominant within the collective of patients between age 50 and 60. The relative magnitudes of the two components were such that a fraction of 55 to 60% of the total of 58 cataracts had to be ascribed to the dose-related indicence. Impaired vision due to cataract was diagnosed before age 54 in 25 cases. In terms of injected activity per unit body weight no depencence of the sensitivity on age was found; specifically there was no indication of a faster occurrence of the treatment-related cataracts in patients treated at older ages.
AU  - Chmelevsky, D.
AU  - Mays, C.W.
AU  - Spieß, H.F.
AU  - Stefani, F.H.
AU  - Kellerer, A.M.
C1  - 42367
C2  - 36185
SP  - 238-257
TI  - An epidemiological assessment of lens opacifications that impaired vision in patients injected with Radium-224.
JO  - Radiat. Res.
VL  - 115
IS  - 2
PY  - 1988
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The yeast mutant rad54-3 is temperature conditional for the rejoining of DNA double-strand breaks, but cells do proliferate at both the restrictive and permissive temperatures. Thus, after irradiation with 30 MeV electrons, survival curves can be obtained which may or may not involve double-strand break rejoining under certain experimental conditions. Because of this special property of rad54-3 cells, it was possible to demonstrate that rejoining of radiation-induced double-strand breaks under nongrowth conditions yields exponeintial survival curves the slopes of which decrease as a function of the rejoining time. These survival data suggest that, under nongrowth conditions, the rejoining of double-strand breaks is an unsaturated process and lacks binary misrepair. In contrast, whenever rejoining of double-strand breaks occurs under growth conditions, shouldered survival curves are observed. This is true for immediate plating as well as for delayed plating survival curves. It is proposed that it is the unsaturated rejoining of double-strand breaks under nongrowth conditions, lacking binary misrepair, which is responsible for potentially lethal damage repair.
AU  - Frankenberg-Schwager, M.
AU  - Frankenberg, D.
AU  - Harbich, R.
C1  - 42205
C2  - 35085
SP  - 54-63
TI  - Exponential or shouldered survival curves result from repair of DNA double-strand breaks depending on postirradiation conditions.
JO  - Radiat. Res.
VL  - 114
IS  - 1
PY  - 1988
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Schäffer, J.B.
AU  - Scherb, H.
AU  - Welzl, G.
C1  - 17789
C2  - 10700
SP  - 437-446
TI  - Frequency Distributions and Density Functions of Distances with Simulated Linear Track Structures.
JO  - Radiat. Res.
VL  - 113
PY  - 1988
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The ability of Ehrlich ascites tumor cells (EAT cells) to repair potentially lethal damage (α-PLD) as demonstrated by either an increase in survival after delayed plating or a decrease in survival after treatment with β-arabinofuranosyladenine (β-araA) was investigated after exposure to protons, deuterons, 3He, 4He, and heavy ions of various specific energies. A significant amount of repair or fixation was observed after delayed plating or treatment with β-araA, respectively, in cells that were exposed to protons of 6-21 MeV energy, reflecting mainly variations in the survival curve shoulder width. Four-hour treatment with 80 μM/liter β-araA resulted in an exponential survival curve for all proton energies tested. A decrease in particle energy increased killing and caused a reduction in D(q) without a significant change in D(O). The survival curve obtained after exposure of cells to 3.4 MeV protons had only a small shoulder and was only slightly modified by either delayed plating or treatment with β-araA, suggesting a decrease in the induction rate of α-PLD. Similar results were also obtained after exposure to deuterons and 4He ions. The results are interpreted as indicating the importance of the specific particle energy and the δ-electron spectrum in the induction of α-PLD. When the results of delayed plating of cells exposed to protons, deuterons, or helium ions were pooled, an exponential relationship between D(q) and penumbra radius was indicated. After exposure to 40Ar ions of 18 MeV specific energy, a shouldered survival curve was obtained, and β-araA significantly enhanced killing by modifying D(q) as well as D(O), a result that also suggests induction of repairable damage by the δ particles produced and interaction of lesions induced within the core of the ion path with penumbra lesions. Based on these results a model is proposed assuming that α-PLD results from interaction, during the course of repair, of pairs of DNA lesions induced within a distanced (i). The model assumes (a) the existence of a critical separation distance d(ic), with the property that pairs of lesions induced with separation distance shorter than d(ic) (expressed as number of base pairs) will always be expressed as lethal, and (b) the existence of a maximum separation distance d(im), with the property that pairs of lesions induced with separation distance larger than d(im) will not interact. Further, it is assumed that the interaction of lesions induced at a distance d(i) such that d(ic) ≤ d(i) ≤ d(im) depends on the postirradiation conditions employed. It is thought that d(i) decreases if cells are kept under conditions preventing proliferation (DP) and that it increases after treatment with β-araA. In both cases variation in d(i) is attributed to treatment-associated alterations in chromatin structure. The observed reduction in the induction of PLD with decreasing particle energy is interpreted as an increase in the fraction of pairs of lesions induced at distances shorter than d(ic), and a concomitant decrease in the fraction of pairs of lesions induced at distances between d(ic) and d(im). These hypothetical lesions are thought either to be located within the particle's penumbra or to arise from combinations of ionizations induced in the particle's core and its penumbra. Finally, the possibility of distinction between LET-dependent effects in D(O) and particle specific energy-dependent effects in D(q) is explored.
AU  - Bertsche, U.
AU  - Ilialus, G.
C1  - 41551
C2  - 36239
SP  - 26-46
TI  - Modifications in repair and expression of potentially lethal damage (α-PLD) as measured by delayed plating or treatment with β-araA in plateau-phase Ehrlich ascites tumor cells after exposure to charged particles of various specific energies.
JO  - Radiat. Res.
VL  - 111
IS  - 1
PY  - 1987
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Cells plated immediately after irradiation on nutrient agar (immediate plating) exhibit a lower survival than cells which are kept under nongrowth conditions before plating (delayed plating). The difference between the survival curves obtained after immediate plating and delayed plating is considered to exhibit the cell's capacity to repair potentially lethal damage. In yeast evidence has been presented previously for the DNA double-strand break (DSB) as the molecular lesion involved in the repair of potentially lethal damage observed at the cellular level. Radiation-induced DSB are repaired in cells plated on nutrient agar, i.e., under growth conditions, as well as in cells kept under nongrowth conditions. In this paper DSB repair under growth and nongrowth conditions is studied with the help of the yeast mutant rad54-3 which is temperature conditional for DSB repair. It is shown that the extent of repair of potentially lethal damage can be varied by shifting the relative fractions of repair of DSB under growth conditions versus nongrowth conditions. Repair of DSB in cells plated on nutrient agar is promoted when glucose is substituted by Na-succinate as an energy source. As a result the immediate plating survival curve approaches the delayed plating survival curve, thus reducing the operationally defined repair of potentially lethal damage. We show that this reduced potentially lethal damage repair is caused, however, by a higher amount of DSB repair in cells immediately plated on succinate agar as compared to glucose agar.
AU  - Frankenberg-Schwager, M.
AU  - Frankenberg, D.
AU  - Harbich, R.
C1  - 41827
C2  - 36238
SP  - 192-200
TI  - Potentially lethal damage repair is due to the difference of DNA double-strand break repair under immediate and delayed plating conditions.
JO  - Radiat. Res.
VL  - 111
IS  - 2
PY  - 1987
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Alkaline phosphatase activity of capillary endothelial cells in the heart of Wistar and Sprague-Dawley rats was studied sequentially after single doses of 10, 15, 20, or 25 Gy. Following irradiation capillary density and alkaline phosphatase activity were focally lost before myocardial degeneration or clinical symptoms of heart disease developed. Recovery from both changes took place after doses of 10 or 15 Gy. The decrease in capillary density and enzyme activity showed the same strain difference in latency times and in the extent of the lesions as previously described for pathological and clinical signs of heart disease.
AU  - Lauk, S.
C1  - 41015
C2  - 40299
SP  - 118-128
TI  - Endothelial alkaline phosphatase activity loss as an early stage in the development of radiation-induced heart disease in rats.
JO  - Radiat. Res.
VL  - 110
IS  - 1
PY  - 1987
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The impact of intracellular glutathion depletion on chromosome damage induced by X irradiation under aerobic conditions was investigated in two different cell lines, Ehrlich ascites tumor cells (EATC) and Chinese hamster ovary cells (CHO-K1). Thiol-depleted cell cultures in plateau phase were obtained by prolonged incubation in growth medium containing DL-buthionine SR-sulfoximine (BSO), a specific inhibitor of γ-glutamyl-cysteine synthetase. Cells were then assayed using the procedures of G. L. Ellmann, F. Tietze, and J. Sedlack & R. H. Lindsay, for non-protein bound SH (NPSH), glutathione (GSH), and total SH (TSH). In both cell lines GSH was reduced to less than 10% of controls at higher BSO concentrations around 1 mM, whereas TSH and NPSH were affected to only 40-60%. In EATC pretreated with up to 1 mM BSO for 72 h, increased levels of spontaneously occurring micronuclei were found. At BSO concentrations above 200 μM, both cell lines showed a potentiation of chromosome lesions scored as micronuclei and induced under aerobic X irradiation when liquid holding recovery in the original nutrient-depleted medium was performed; the extent of chromosome damage eventually reached that which could be obtained by application of β-arabinofuranosyladenine (β-araA), known to inhibit DNA repair processes by blocking DNA polymerases. It is therefore suggested that GSH depletion causes impairment of repair of lesions leading to chromosome deletions and subsequently to micronuclei. In contrast to CHO cell cultures, EATC showed a reversion of the potentiation effect as indicated by a decrease in the micronucleus content during prolonged incubation in the presence of BSO in the millimolar range. This effect could not be correlated to the remaining GSH content of less than 10% but may be due to some accumulation of unknown NPSH components. Since addition of L-cysteine to EATC cultures pretreated with BSO decreased the micronucleus content, cysteine/cystine or a related thiol within the NPSH fraction may be involved in the reestablishment of repair. Thus at least in one cell line, a rather complex response to BSO administration indicated that not only GSH but also other thiols may determine the level of chromosome damage after liquid holding recovery.
AU  - Bertsche, U.
AU  - Schorn, H.
C1  - 33544
C2  - 36123
SP  - 351-369
TI  - Glutathione depletion by DL-buthionine-SR-sulfoximine (BSO) potentiates X-ray-induced chromosome lesions after liquid holding recovery.
JO  - Radiat. Res.
VL  - 105
IS  - 3
PY  - 1986
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The W value, the mean energy required to form an ion pair, was measured for monoenergetic positive H, He, C, N, O, and Ar ions in the energy range from 1 to 50 keV in air, N2, CH4, CO2, and a tissue-equivalent gas (Rossi-Failla mixture). The W values of ions increase, in general, with decreasing energy; only those of H ions show a minimum at an energy of about 25 keV for some gases. The estimated standard deviation of the measurements is about 2% in most cases.
AU  - Huber, R.M.
AU  - Combecher, D.
AU  - Burger, G.T.
C1  - 41724
C2  - 38275
SP  - 237-251
TI  - Measurement of average energy required to produce an ion pair (W value) for low-energy ions in several gases.
JO  - Radiat. Res.
VL  - 101
IS  - 2
PY  - 1985
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Survival data on yeast cells proficient or deficient in the repair of DNA double-strand breaks (dsb) and data on the induction of dsb are used to interpret the dose dependence of the RBE value for lethal lesions after irradiation at high dose rate followed by 72-hr liquid holding providing optimum conditions for repair of potentially lethal lesions (RBE(DP), DP = delayed plating). The radiations applied are conventional (150 kV), soft (50 kV), and ultrasoft (4 kV) X rays, 30-MeV electrons (or 60Co γ rays), and 3.5-MeV α particles. Analysis shows that the dose dependence of the RBE(DP) value can be explained by the combination of two dose-independent RBE values, one for the single-particle traversal effect (RBE(spt)) and the other for the accumulation of dsb (RBE(dsb)) due to the traversal of more than one particle through the cell nucleus. Furthermore, it is shown that the LET dependence of RBE(spt) values describing the linear component of the lethal lesions must be considered separately for 'electron' and 'particle' radiations.
AU  - Frankenberg, D.
C1  - 41568
C2  - 38417
SP  - 329-340
TI  - Interpretation of the dose and LET dependence of RBE values for lethal lesions in yeast cells.
JO  - Radiat. Res.
VL  - 97
IS  - 2
PY  - 1984
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Cell killing and the induction of mutation to thioguanine resistance (HGPRT enzyme deficiency) were measured after exposure of Ehrlich ascites tumor cells to 150-kV X rays and 241Am α particles. The curve describing the induction of mutations was almost linear after exposure to α particles (slope: 14.1 x 10-5 Gy-1) but upward bending after exposure to X rays, apparently reaching a final slope similar to that obtained after exposure to α particles. The number of mutants induced per viable cell by α particles at a given level of cell killing was similar to that induced by X rays. The RBE values obtained for cell killing and the induction of mutations are compared with each other, and the possible involvement of repair processes in determining the RBE is discussed.
AU  - Iliakis, G.E.
C1  - 41434
C2  - 38421
SP  - 52-58
TI  - The mutagenicity of alpha particles in Ehrlich ascites tumor cells.
JO  - Radiat. Res.
VL  - 99
IS  - 1
PY  - 1984
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - This series of investigations was designed to observe growth and division of single, diploid yeast cells within the first four generations after irradiation with ionizing radiation. Evidence exists that cell reactions important for the final cell fate occur during this period, and therefore the analysis of cell kinetics and of stationary forms of inactivated cells can be performed. A large number of experiments is necessary to obtain statistically confirmed results of single-cell observation. An automatically steered microphotographic registration device has been developed to facilitate the collection of large numbers of observations. Optical data scanned by a TV camera and digitally stored in a computer are processed by pattern recognizing programs to achieve the correct correlation of newly built cells to existing ones and to deliver a pedigree over four generations of at least eight cells for every irradiated single cell. The pooled data of many pedigrees of this kind allow the analysis of the differential behavior of a total population. From the analysis of X-irradiated cells one can conclude that a single cell that produces at least a microcolony of five cells is eventually able to form a macrocolony and thus can be considered a survivor. That means the division probability of cells to go from generation zero to three corresponds to the survival curve of the colony-forming ability test. Therefore this method is suitable for the differential description of the important phenomenological cell reactions after irradiation.
AU  - Grundler, W.
AU  - Abmayr, W.
C1  - 41451
C2  - 40317
SP  - 464-479
TI  - Differential inactivation analysis of diploid yeast exposed to radiation of various LET. I. Computerized single-cell observation and preliminary application to X-ray-treated Saccharomyces cervisiae.
JO  - Radiat. Res.
VL  - 94
IS  - 3
PY  - 1983
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The survival of synchronously growing Ehrlich ascites tumor cells (EAT cells) was measured after X irradiation in various stages of the cell cycle. Cells at the beginning of S or in G2 + M phase showed a high level of killing, whereas cells irradiated in G1 or in the middle of S phase were more resistant. These changes resulted fom a change in the survival curve shoulder width (D(q)) as cells passed through the cell cycle, and the mean lethal dose (D(0)) remained practically unchanged (0.8 ± 0.05 Gy). When synchronization of the cell population was further sharpened using nocodazole, exponential survival curves were obtained at the beginning of S phase and at mitosis with a D(0) = 0.8 Gy. When cells (in all stages) were incubated in balanced salt solution for 6 hr after irradiation, repair of potentially lethal damage (PLD) was observed, resulting in an increase in D(q), while D(0) remained constant. Treatment of the cells after irradiation with either caffeine (2-6 mM) or β-arabinofuranosyladenine (β-araA) (60-100 μM) or hypertonic medium resulted in an expression of PLD and reduced the D(q) of the survival curve, which approached or reached an exponential line with D(0) = 0.8 ± 0.1 Gy. We measured the rate of the loss of sensitivity of these treatments that we assume reflects the rate of repair of PLD. For caffeine (6 mM) treatment (S cells, 5 hr) we found a repair time constant (t50) or about 1 hr, similar to that observed for repair of PLD in growth medium containing 0.5 μg/ml aphidicolin. With hypertonic treatment we detected two repair components, a fast one that restored the slope of the survival curve, and a slow one with a t50 of about 1 hr that restored the shoulder of the survival curve. PLD induced by irradiating in G1 phase was repaired when cells were arrested for some hours either in G1 phase or in the subsequent mitosis but was not repaired if the cells were arrested in S phase. PLD induced in S or G2 + M phase was repaired only when the cells were arrested in the cell cycle before division. Results indicate that the shoulder width D(q) of the survival curve in cells irradiated at various stages of the cell cycle results from repair of PLD. This repair of PLD probably takes place in the interval between irradiation and the next S phase or mitosis and is therefore minimal for cells irradiated at the G1/S border or in mitosis (D(q) = 0). PLD still unrepaired when the cells reach these phases is assumed to be expressed, as was found for PLD repaired in cells incubated in balanced salt solution, for some hours after irradiation. We therefore suggest that the variations observed in cell survival through the cell cycle might reflect variations in the final amount of PLD either repaired or expressed as the cells progress through the various stages of the cell cycle.
AU  - Iliakis, G.E.
AU  - Nüsse, M.
C1  - 42234
C2  - 38362
SP  - 87-107
TI  - Evidence that repair and expression of potentially lethal damage cause the variations in cell survival after X irratiation observed through the cell cycle in Ehrlich ascites tumor cells.
JO  - Radiat. Res.
VL  - 95
IS  - 1
PY  - 1983
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Irradiation of diploid yeast cells with 30-MeV electrons at a high dose rate (130 Gy/min) was previously shown to yield a linear-quadratic function between irreparable double-strand breaks and dose. The quadratic term is reduced when irradiation is performed with 60Co γ rays at a low dose rate (0.55 Gy/min). This effect of dose rate at the level of double-strand breaks correlates with that previously found at the level of colony-forming ability of yeast cells irradiated in the same dose range. By analogy with the results obtained in survival studies it is proposed that the linear component of the relationship between irreparable double-strand breaks and dose is due to a single track of an electron of medium energy, whereas the quadratic component is caused by the cooperative effect of track ends, each of which is produced by a separate traversal of a slow electron through the yeast nucleus.
AU  - Frankenberg-Schwager, M.
AU  - Frankenberg, D.
AU  - Bloecher, D.
AU  - Adamczyk, C.
C1  - 41308
C2  - 40366
SP  - 710-717
TI  - Effect of dose rate on the induction of DNA double-strand breaks in eukaryotic cells.
JO  - Radiat. Res.
VL  - 87
IS  - 3
PY  - 1981
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - During the usual procedure of testing cell survival by colony-forming ability, repair of potentially lethal damage (PLD) takes place. By incubating the cells in hypertonic suspension a certain part of this repair can be inhibited, leading to an exponential dose-survival curve as expected from the Poisson distribution of lethal events in the cells. If such a hypertonic treatment is performed after increasing intervals following irradiation with X rays, curves with increasing shoulder length are obtained. Quantitative analysis of the kinetics of this repair shows that PLD is repaired for about 1 hr after irradiation by a saturated repair system which eliminates about one lesion per 15 min per cell independent of the applied absorbed dose. PLD not eliminated by this 'fast' system is repaired by an unsaturated system with a time constant of several hours. Repair of PLD after X irradiation proceeds quantitatively in this way in plateau-phase cells suspended in a conditioned medium, which seems optimal for such repair. If these cells are suspended after irradiation in normal nutrient medium a certain fraction of the PLD is transformed into irreparable damage. The final survival after repair in nutrient medium is then identical with that obtained by the usual measurement of colony-forming ability on nutrient agar. This indicates that the shoulder in dose-survival curves for plateau-phase cells is partly due to repair of PLD and partly due to manifestation of this damage during repair time.
AU  - Pohlit, W.
AU  - Heyder, I.R.
C1  - 41857
C2  - 38424
SP  - 613-634
TI  - The shape of dose-survival curves for mammalian cells and repair of potentially lethal damage analyzed by hypertonic treatment.
JO  - Radiat. Res.
VL  - 87
IS  - 3
PY  - 1981
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - The W value, the mean energy required to form an ion pair, was measured for monoenergetic electrons in the energy range from 5 to about 500 eV in air, N2, O2, CO2, tissue-equivalent gases (Rossi-Failla and Srdoc mixtures), methane, ethane propane, n-butane, i-butane, pentane, hexane, nonane, ethylene, acetylene, ethanol, acetone, H2O, D2O, H2, D2, C6H6, C6D6, argon, krypton, and xenon. The W values of all gases increase continuously with decreasing electron energy; they approach infinity asymptotically at the ionization threshold and the well-known energy-independent high-energy W values at high electron energies. A comparison between the results and newer experimental and theoretical works of other authors sometimes shows very good agreement. The experimental error is estimated to be less than 2%.
AU  - Combecher, D.
C1  - 33327
C2  - 38418
SP  - 189-218
TI  - Measurement of w values of low-energy electrons in several gases.
JO  - Radiat. Res.
VL  - 84
IS  - 2
PY  - 1980
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - We show that in diploid yeast radiation-induced DNA double-strand breaks can be repaired under nongrowth conditions at 30°C and that liquid holding recovery of colony-forming ability is accompanied by a decrease in the number of double-strand breaks per cell. The kinetics of double-strand break repair under nongrowth conditions depend on the dose applied. For the highest dose used (2400 Gy) repair is completed within about 48 hr. We have verified that double-strand breaks which remain unrepaired after 48 hr are irreparable under nongrowth conditions. The linear relationship between the initial number of double-strand breaks and dose is converted into a quadratic function of irreparable double-strand breaks with and dose during liquid holding treatment of cells.
AU  - Frankenberg-Schwager, M.
AU  - Frankenberg, D.
AU  - Bloecher, D.
AU  - Adamczyk, C.
C1  - 40935
C2  - 38542
SP  - 498-510
TI  - Repair of DNA double-strand breaks in irradiated yeast cells under nongrowth conditions.
JO  - Radiat. Res.
VL  - 82
IS  - 3
PY  - 1980
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Proliferation of lethally damaged tumor cells was determined after irradiation with fast electrons, fast neutrons, α particles, and pions in the peak and plateau of the depth dose curve. The method used was measurement of the proliferation of the total population, N(tot), and the subpopulation of viable cells which are able to grow to macrocolonies after irradiation, N(m). The difference between these populations (N(tot) - N(m)) then represents the lethally damaged cells. The number of cell divisions after irradiation decreases with increasing absorbed dose in the same way for all the different types of radiation if related to the survival of cells, S. Consequences for the type of lethal radiation damage in mammalian cells and for radiotherapy are discussed.
AU  - Heyder, I.R.
AU  - Pohlit, W.
C1  - 33017
C2  - 35547
SP  - 352-363
TI  - Proliferation of lethally damaged mammalian cells irradiated by fast electrons, fast neutrons, α particles, and pions.
JO  - Radiat. Res.
VL  - 82
IS  - 2
PY  - 1980
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Stationary populations of diploid yeast (Saccharomyces cerevisiae, wild type, strain No. 211) were irradiated with sparsely and densely ionizing radiations at high and in part at low dose rates. Mean LET values ranged from 0.1 to 600 keV/μm. The reproductive capacity of the cells was measured by macrocolony counting. After irradiation at high dose rates, agar-holding reactivation was allowed for 48 hr. Dose-effect curves showed a change from sigmoidal to exponential form with increasing LET and a maximum of the slope of the exponential part at about 70 keV/μm. If the radiation response at higher doses is separated into contributions of potentially lethal and of lethal damage, one finds different dependence on the mean LET. The observed lethal damage production is discussed in terms of single-hit events expected from theoretical considerations.
AU  - Bertsche, U.
C1  - 40951
C2  - 40441
SP  - 349-367
TI  - The response of diploid yeast to radiations at different LET. I. Potentially lethal and lethal damage to reproductive capacity.
JO  - Radiat. Res.
VL  - 76
IS  - 2
PY  - 1978
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Low doses of X rays and uv light delivered at low dose rates stimulated the tube growth of Pinus silvestris pollen, while sublethal doses supplied at moderate dose rates inhibited the tube growth significantly. The irradiation also altered the level of ribosome content. The polysome content measured after 72 hr of tube development was twice as high in samples irradiated with sublethal doses as in samples irradiated with low doses. The control samples possessed only light oligosomes, while in low-dose irradiated samples all polysomes were heavy polysomes, and in sublethally irradiated samples only 20% of polysomes were heavy polysomes. The irradiated pollen, incubated for more than 56 hr, incorporated more uridine than the control: The low dose samples had twice as much labeled uridine in the rRNA as the sublethally irradiated samples.
AU  - Zelles, L.
C1  - 42434
C2  - 40438
SP  - 633-645
TI  - Effect of low and sublethal doses of irradiation on the ribosome content and on the incorporation of [3H]uridine into the RNA of growing tubes of pine pollen.
JO  - Radiat. Res.
VL  - 76
IS  - 3
PY  - 1978
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - Osteocytes from the proximal tibial metaphysis of mice were examined by electron microscopy at various time intervals after the incorporation of 1, 1.5, or 5 μCi/kg of body weight 224Ra. The animals were sacrificed 2 hr, 24 hr, or 5 days following administration of the short lived bone seeking radionuclide. Only the younger, osteoblast like osteocytes from the undecalcified trabecular bone were studied. Compared with the osteocytes from bone tissue of control animals, about half of the cells examined in specimens from animals treated with 224Ra showed ultrastructural alterations. In the nuclei of many osteocytes the chromatin was condensed. The mitochondria showed various signs of damage such as loss of cristae, swelling, and dissociation or disruption of both limiting membranes. Additionally, giant mitochondria were found. The rough surfaced endoplasmic reticulum was sometimes dilated and formed large cisternae. The Golgi complex was vacuolated. The pericellular spaces of lacunae containing severely damaged osteocytes were enlarged. It is thought that the early ultrastructural changes in osteocytes from the trabecular bone of mice resulted from the effects of direct irradiation upon the cells. Probably, all osteocytes which showed lesions were situated within the range of the α radiation emitted from the incorporated 224Ra which was randomly distributed in the mineralized bone matrix of the trabeculae. The mitochondria of the osteoblast like osteocytes appeared to be the cellular organelles most sensitive to the effects of 224Ra administration.
AU  - Marquart, K.H.
C1  - 33022
C2  - 40437
SP  - 40-53
TI  - Metaphysis of mice after the incorporation of 224Ra.
JO  - Radiat. Res.
VL  - 69
IS  - 1
PY  - 1977
SN  - 0033-7587
ER  - 

TY  - JOUR
AB  - 224Ra was applied with one single injection or with repeated injections (twice weekly over various time periods, up to 36 wk). In general the bone tumor incidence increased with dose but with the restriction that the maximum instantaneous dose rate be not too high. The 1080 rad total skeletal dose thus resulted in a bone tumor incidence between 15 and 90% depending on the length of the injection spans. These results were compared with the effect of singly injected long lived 226Ra, using data by M. Finkel et al. It was observed that the specific bone tumor production by 226Ra, expressed as incidence per unit of total accumulated skeletal dose, was steadily diminished with an increase of the dose. As a consequence, it was found that mice after a single injection of the long lived 226Ra within the tested dose range had in general a considerably lower bone tumor incidence than those mice having received comparable skeletal doses through repeated injections of the short lived 224Ra over a longer period.
AU  - Müller, W.A.
AU  - Luz, A.
C1  - 41320
C2  - 40411
SP  - 444-448
TI  - The osteosarcomogenic effectiveness of the short lived 224Ra compared with that of the long lived 226Ra in mice.
JO  - Radiat. Res.
VL  - 70
IS  - 2
PY  - 1977
SN  - 0033-7587
ER  - 

TY  - JOUR
AU  - Mueller, W.A.
AU  - Goessner, W.
AU  - Hug, O.
C1  - 42385
C2  - 40393
SP  - 55
TI  - Dosimetric aspects after repeated injections of short lived alpha emitters in mice with regard to the risk of late effects.
JO  - Radiat. Res.
VL  - 59
IS  - 1
PY  - 1974
SN  - 0033-7587
ER  -