Mechanistic modelling of oxygen enhancement ratio of radiation via Monte Carlo simulation-based DNA damage calculation

Objective. Oxygen plays an important role in affecting the cellular radio-sensitivity to ionizing radiation. The objective of this study is to build a mechanistic model to compute oxygen enhancement ratio (OER) using a GPU-based Monte Carlo (MC) simulation package gMicroMC for microscopic radiation transport simulation and DNA damage calculation. Approach. We first simulated the water radiolysis process in the presence of DNA and oxygen for 1 ns and recorded the produced DNA damages. In this process, chemical reactions among oxygen, water radiolysis free radicals and DNA molecules were considered. We then applied a probabilistic approach to model the reactions between oxygen and indirect DNA damages for a maximal reaction time of t (0). Finally, we defined two parameters P (0) and P (1), representing probabilities for DNA damages without and with oxygen fixation effect not being restored in the repair process, to compute the final DNA double strand breaks (DSBs). As cell survival fraction is mainly determined by the number of DSBs, we assumed that the same numbers of DSBs resulted in the same cell survival rates, which enabled us to compute the OER as the ratio of doses producing the same number of DSBs without and with oxygen. We determined the three parameters (t (0), P (0) and P (1)) by fitting the OERs obtained in our computation to a set of published experimental data under x-ray irradiation. We then validated the model by performing OER studies under proton irradiation and studied model sensitivity to parameter values. Main results. We obtained the model parameters as t (0) = 3.8 ms, P (0) = 0.08, and P (1) = 0.28 with a mean difference of 3.8% between the OERs computed by our model and that obtained from experimental measurements under x-ray irradiation. Applying the established model to proton irradiation, we obtained OERs as functions of oxygen concentration, LET, and dose values, which generally agreed with published experimental data. The parameter sensitivity analysis revealed that the absolute magnitude of the OER curve relied on the values of P (0) and P (1), while the curve was subject to a horizontal shift when adjusting t (0). Significance. This study developed a mechanistic model that fully relies on microscopic MC simulations to compute OER.