Stochastic modelling of DSB repair after photon and ion irradiation.

PURPOSE: To test the stochastic model for DNA double-strand break (DSB) repair via non-homologous end joining (NHEJ) implemented in the Monte Carlo code PARTRAC (PARticle TRACks) against measured repair kinetics after nitrogen ion and (60)Co γ reference irradiation.
MATERIAL AND METHODS: By combining Monte Carlo track structure calculations with multi-scale models of cellular DNA, yields of DSB are calculated for N ion and (60)Co γ-irradiation. The NHEJ model in PARTRAC is used to determine rejoining kinetics of the DNA ends and DNA fragment distributions after certain repair times. Model parameters are adapted to the measured rejoining kinetics for the different radiation types.
RESULTS: DSB rejoining kinetics after low- and high-linear energy transfer (LET) irradiation have been reproduced after refinements of the DNA repair model, in particular by considering an ongoing production of detectable DSB in the initial phase, e.g., by enzymatic processing of labile sites, and by assuming a limited availability of repair enzymes needed for processing complex lesions during the slow repair phase.
CONCLUSIONS: The need for certain model refinements suggests mechanisms that may significantly contribute to the DSB rejoining kinetics during both initial and later phases of NHEJ.