TY  - JOUR
AB  - Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100 mSv and dose rates of <10 mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30–60 mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low Dose Research towards Multidisciplinary Integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles.
AU  - Hall, J.*
AU  - Jeggo, P.A.*
AU  - West, C.*
AU  - Gomolka, M.*
AU  - Quintens, R.*
AU  - Badie, C.*
AU  - Laurent, O.*
AU  - Aerts, A.L.*
AU  - Anastasov, N.
AU  - Azimzadeh, O.
AU  - Azizova, T.V.*
AU  - Baatout, S.*
AU  - Baselet, B.*
AU  - Benotmane, M.A.*
AU  - Blanchardon, E.*
AU  - Guéguen, Y.*
AU  - Haghdoost, S.*
AU  - Harms-Ringhdahl, M.*
AU  - Hess J.
AU  - Kreuzer, M.*
AU  - Laurier, D.*
AU  - Macaeva, E.*
AU  - Manning, G.*
AU  - Pernot, E.*
AU  - Ravanat, J.L.*
AU  - Sabatier, L.*
AU  - Tack, K.*
AU  - Tapio, S.
AU  - Zitzelsberger, H.
AU  - Cardis, E.*
C1  - 50450
C2  - 42477
CY  - Amsterdam
SP  - 59-84
TI  - Ionizing radiation biomarkers in epidemiological studies – An update.
JO  - Mutat. Res.- Rev. Mutat. Res.
VL  - 771
PB  - Elsevier Science Bv
PY  - 2017
SN  - 1383-5742
ER  - 

TY  - JOUR
AB  - The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2. Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.
AU  - Ainsbury, E.A.*
AU  - Barnard, S.*
AU  - Bright, S.*
AU  - Dalke, C.
AU  - Jarrin, M.*
AU  - Kunze, S.
AU  - Tanner, R.*
AU  - Dynlacht, J.R.*
AU  - Quinlan, R.A.*
AU  - Graw, J.
AU  - Kadhim, M.*
AU  - Hamada, N.*
C1  - 50047
C2  - 42001
CY  - Amsterdam
SP  - 238-261
TI  - Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.
JO  - Mutat. Res.- Rev. Mutat. Res.
VL  - 770
PB  - Elsevier Science Bv
PY  - 2016
SN  - 1383-5742
ER  - 

TY  - JOUR
AB  - Epidemiological studies on the atomic-bomb survivors, cancer survivors and occupational cohorts provide strong evidence for multifaceted damage to brain after ionizing radiation. Radiation-induced late effects may manifest as brain tumors or cognitive impairment. Decreased neurogenesis and differentiation, alteration in neural structure and synaptic plasticity as well as increased oxidative stress and inflammation are suggested to contribute to adverse effects in the brain. In addition to neural stems cells, several brain-specific mature cell types including endothelial and glial cells are negatively affected by ionizing radiation. Radiation-induced enhancement of endothelial cell apoptosis results in disruption of the vascular system and the blood brain barrier. Activated microglia create inflammatory environment that negatively affects neuronal structures and results in decreased synaptic plasticity. Although the molecular mechanisms involved in radiation-induced brain injury remain elusive, first strategies for prevention and amelioration are being developed. Drug-based prevention and treatment focus mainly on the inhibition of oxidative stress and inflammation. Cell replacement therapy holds great promise as first animal studies using transplantation of neural stem cells to irradiated brain have been successful in restoring memory and cognition deficits. This review summarizes the epidemiological and biological data on radiation-induced brain damage and describes prevention and therapy methods to avoid and ameliorate these adverse effects, respectively.
AU  - Hladik, D.
AU  - Tapio, S.
C1  - 50106
C2  - 42021
CY  - Amsterdam
SP  - 219-230
TI  - Effects of ionizing radiation on the mammalian brain.
JO  - Mutat. Res.- Rev. Mutat. Res.
VL  - 770
PB  - Elsevier Science Bv
PY  - 2016
SN  - 1383-5742
ER  - 

TY  - JOUR
AB  - It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5–5 Gy) is suggestive and weak after low doses (<0.5 Gy). However, evidence is emerging that doses under 0.5 Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5 Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases.
AU  - Kreuzer, M.*
AU  - Auvinen, A.*
AU  - Cardis, E.*
AU  - Hall, J.*
AU  - Jourdain, J.R.*
AU  - Laurier, D.*
AU  - Little, M.P.*
AU  - Peters, A.
AU  - Raj, K.*
AU  - Russell, N.S.*
AU  - Tapio, S.
AU  - Zhang, W.*
AU  - Gomolka, M.*
C1  - 44851
C2  - 37024
CY  - Amsterdam
SP  - 90-100
TI  - Low-dose ionising radiation and cardiovascular diseases – strategies for molecular epidemiological studies in Europe.
JO  - Mutat. Res.- Rev. Mutat. Res.
VL  - 764
PB  - Elsevier Science Bv
PY  - 2015
SN  - 1383-5742
ER  - 

TY  - JOUR
AB  - Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.
AU  - Pernot, E.*
AU  - Hall, J.*
AU  - Baatout, S.*
AU  - Benotmane, M.A.*
AU  - Blanchardon, E.*
AU  - Bouffler, S.*
AU  - El Saghire, H.*
AU  - Gomolka, M.
AU  - Guertler, A.
AU  - Harms-Ringdahl, M.*
AU  - Jeggo, P.*
AU  - Kreuzer, M.
AU  - Laurier, D.*
AU  - Lindholm, C.*
AU  - Mkacher, R.*
AU  - Quintens, R.*
AU  - Rothkamm, K.*
AU  - Sabatier, L.*
AU  - Tapio, S.
AU  - de Vathaire, F.*
AU  - Cardis, E.*
C1  - 10481
C2  - 30217
SP  - 258-286
TI  - Ionizing radiation biomarkers for potential use in epidemiological studies.
JO  - Mutat. Res.- Rev. Mutat. Res.
VL  - 751
IS  - 2
PB  - Elsevier
PY  - 2012
SN  - 1383-5742
ER  -