Combined use of Monte Carlo DNA damage simulations and deterministic repair models to examine putative mechanisms of cell killing.

Abstract Carlson, D. J., Stewart, R. D., Semenenko, V. A. and Sandison, G. A. Combined Use of Monte Carlo DNA Damage Simulations and Deterministic Repair Models to Examine Putative Mechanisms of Cell Killing. Radiat. Res. 169, 447–459 (2008). A kinetic repair-misrepair-fixation (RMF) model is developed to better link double-strand break (DSB) induction to reproductive cell death. Formulas linking linear-quadratic (LQ) model radiosensitivity parameters to DSB induction and repair explicitly account for the contribution to cell killing of unrejoinable DSBs, misrepaired and fixed DSBs, and exchanges formed through intra- and intertrack DSB interactions. Information from Monte Carlo simulations is used to determine the initial yields and complexity of DSBs formed by low- and high-LET radiations. Our analysis of published survival data for human kidney cells suggests that intratrack DSB interactions are negligible for low-LET radiations but increase rapidly with increasing LET. The analysis suggests that no cl...