22 Décembre – Thesis defense - Wook Geun Shin

08 h Full videoconferencing

Development and application of the Geant4-DNA toolkit for the simulation of biological damage at the sub-cellular scale.

Predicting the biological effects induced by ionizing radiation is a major scientific challenge of current radiobiology, in particular to try to better understand the effects of low doses on living beings as well as carcinogenesis. The computational approach based on codes to simulate trace structures in the biological medium using the Monte Carlo technique is today the most reliable method to calculate the early effects of ionizing radiation on DNA, the main cellular target of radiation effects. Among the existing codes, the Geant4-DNA extension of the Geant4 general purpose simulation toolkit is the first one fully open and freely available to the community. Geant4-DNA can simulate not only the physical but also the physico-chemical and chemical stages of water radiolysis. These stages can be combined with simplified geometric models of DNA to assess direct and indirect early DNA damage. In this thesis, I propose (1) to improve in Geant4-DNA the modeling of the elastic scattering of electrons in liquid water in order to simulate more precisely the spatial distribution of energy deposits and radical species. Then, (2) the physico-chemical stage of water radiolysis is also improved based on approaches described in the literature (modeling, measurements), this step strongly affecting the chemical stage by modifying the initial yields and the concentration of radical species. (3) In addition, the Independent Reaction Time (IRT) method is implemented in Geant4-DNA to reduce the computational time to simulate the chemical kinetics of water radiolysis. Finally, I evaluate (4) the biological damage induced at the subcellular scale using a cellular DNA geometry developed in a previous study, including in the simulation all the improvements developed during this thesis, up to the repair of early DNA damage. These developments are grouped in a complete simulation chain for users of the Geant4-DNA extension of Geant4.

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