With the increasing exposure of humans to densely ionizing radiation for space or hadron therapy applications, it is of fundamental importance to understand the multiscale radiation-induced effects for radioprotection and treatment planning purposes. Thus, this study will represent an important step in this process by assessing the radiation-induced DNA damage using computational tools for various exposure scenarios (electrons, photons, ions) and different target definition (entire cell nucleus, simple DNA string…). The calculations will be performed employing the computer codes TOPAS-nBIO (Schuemann et al., 2018) and MCDS (Semenenko and Stewart, 2004), and systematically investigating the effect of varying and co-varying the simulation parameters. The validation of the obtained results will be performed through a comparison against literature in vitro data and other track structure simulations.
Structure of the study
- Get familiar with the mechanisms underlying the radiation-induced damaging process at different scales and its effect on living entities (DNA damage and repair, chromosome aberrations, cell survival).
- Create a database of DNA-damage (SSB, DSB, DSB cluster…), DNA-repair and chromosome aberrations by extracting the results of published in vitro and in silico published studies. The database will later serve as a validation tool for the data obtained during this work.
- Perform the simulations of the initial DNA-damage using the TOPAS-nBIO and MCDS codes investigating the combined effect of varying:
- the radiation quality (electrons, photons and ions)
- the DNA damage scoring method (threshold or linear probability)
- the production of radical species
- the macro- and microscopic target definition
- the hypoxia level (oxygen availability within the target volume)
- the simulation code
- Validate the results against the initial-DNA damage data of point 2)
- Assess the performances of existing or ad hoc developed DNA repair models in comparison with the repair-kinetics data of point 2).
- Analyze the pattern of residual DNA damage in relation to their spatial distribution and the correlation with higher-level endpoints and DNA fragmentations, chromosome aberration and cell survival.
- Write a report/thesis
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