Monte Carlo damage models of different complexity levels predict similar trends in radiation induced DNA damage

Abstract

Ion therapies have an increased relative biological effectiveness (RBE) compared to X-rays, but this remains poorly quantified across different radiation qualities. Mechanistic models that simulate DNA damage and repair after irradiation could be used to help better quantify RBE. However, there is large variation in model design with the simulation detail and number of parameters required to accurately predict key biological endpoints remaining unclear. This work investigated damage models with varying detail to determine how different model features impact the predicted DNA damage.

Methods: Damage models of reducing detail were designed in TOPAS-nBio and Medras investigating the inclusion of chemistry, realistic nuclear geometries, single strand break damage, and track structure. The nucleus models were irradiated with 1 Gy of protons across a range of linear energy transfers (LETs). Damage parameters in the models with reduced levels of simulation detail were fit to proton double strand break (DSB) yield predicted by the most detailed model. Irradiation of the optimised models with a range of radiation qualities was then simulated, before undergoing repair in the Medras biological response model.

Results: Simplified damage models optimised to proton exposures predicted similar trends in DNA damage across radiation qualities. On average across radiation qualities, the simplified models experienced an 8% variation in double strand break (DSB) yield but a larger 28% variation in chromosome aberrations. Aberration differences became more prominent at higher LETs, with model features having an increasing impact on the distribution and therefore misrepair of DSBs. However, overall trends remained similar with better agreement likely achievable through repair model optimisation. 

Conclusion: Several model simplifications could be made without compromising key damage yield predictions, although changes in damage complexity and distribution were observed. This suggests simpler, more efficient models may be sufficient for initial radiation damage comparisons, if validated against experimental data.&#xD.

Keywords: DNA damage; DNA repair; Monte Carlo; Proton; Radiation biology.