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Barbieri, S.* ; Babini, G.* ; Morini, J.* ; Friedland, W. ; Buonanno, M.* ; Grilj, V.* ; Brenner, D.J.* ; Ottolenghi, A.* ; Baiocco, G.*

Predicting DNA damage foci and their experimental readout with 2D microscopy: A unified approach applied to photon and neutron exposures.

Sci. Rep. 9:14019 (2019)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
The consideration of how a given technique affects results of experimental measurements is a must to achieve correct data interpretation. This might be challenging when it comes to measurements on biological systems, where it is unrealistic to have full control (e.g. through a software replica) of all steps in the measurement chain. In this work we address how the effectiveness of different radiation qualities in inducing biological damage can be assessed measuring DNA damage foci yields, only provided that artefacts related to the scoring technique are adequately considered. To this aim, we developed a unified stochastic modelling approach that, starting from radiation tracks, predicts both the induction, spatial distribution and complexity of DNA damage, and the experimental readout of foci when immunocytochemistry coupled to 2D fluorescence microscopy is used. The approach is used to interpret gamma-H2AX data for photon and neutron exposures. When foci are reconstructed in the whole cell nucleus, we obtain information on damage characteristics "behind" experimental observations, as the average damage content of a focus. We reproduce how the detection technique affects experimental findings, e.g. contributing to the saturation of foci yields scored at 30 minutes after exposure with increasing dose and to the lack of dose dependence for yields at 24 hours.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Double-strand Breaks; Track-structure; Histone H2ax; Monte-carlo; Radiation Quality; Gamma-h2ax Foci; Particle; Repair; Model; Mdc1
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 14019 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Medicine (IRM)