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Evaluation, from nanodosimetric simulations, of the chromatin compaction influence on early DNA damage and extension to late effects (functional changes and tell killing)

​Nicolas Tang has defended his thesis on 2nd October 2019 at IRSN, in Fontenay-aux-Roses (France)

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Research Unit > IRSN/PRP-HOM/SDE/LDRI

Authors > TANG Nicolas

Publication Date > 02/10/2019

Summary

This thesis work is part of a fundamental research aimed at improving the understanding of the mechanisms of interaction of ionizing radiation with biological matter by focusing on the prediction of early radiation-induced DNA damage by numerical simulations.

As a first step, a study on the role of the different levels of chromatin compaction (heterochromatin and euchromatin) in the induction of these early effects, namely DNA strand breaks, is proposed. New realistic geometric models of cell nuclei integrating chromatin compaction have therefore been created and used in a calculation chain, based on the open source and general purpose Monte Carlo code Geant4 and its extension Geant4-DNA, to simulate the physical, physico-chemical and chemical stages leading to strand breaks. Developments in this thesis have also allowed studying the impact of several types of radiation (protons, alphas, photons) on radiation-induced damage. The various results were compared with experimental data and in particular those obtained by the IRSN team of radiobiologists. Finally, a study on later effects such as DNA repair and cell death was carried out using both the calculation chain and some parametric models from the literature. Thus, the results obtained in this thesis have made it possible to acquire new knowledge and to develop calculation tools that will soon be deliverd in free access to the scientific community in order to prdict the biological effects of several types of radiation with the aim of improving risk models.
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