Monte Carlo Simulations of DNA Damage and Cellular Response to Hadron Irradiation

Abstract

Numerical simulations are performed on a stochastic model based on Monte Carlo damage simulation process and Markov Chain Monte Carlo techniques to investigate the formation and evaluation of isolated and multiple DNA damage and cellular survival by light ionizing radiation in a colony of tumour cells. The contribution of the local clustering of the strand breaks and base damage is taken into account while considering double-strand breaks (DSBs) as primary lesions in the DNA of the cell nucleus induced by ionizing radiation. The model incorporates the combined effects of biological processes such as the tumour oxygenation, cellular multiplication and mutation through various probability distributions in a full Monte Carlo simulation of fractionated hadrontherapy. Our results indicate that the linear and quadratic parameters of the model show a negative correlation, for protons and helium ions, which might suggest an underlying biological mechanism. Despite using a model with quite different descriptions of linear and quadratic parameters, the observed results for linear parameter show largely reasonable agreement while the quadratic parameter consistent deviations from the results obtained using the LEM model at low LET. In addition to the LET dependence, RBE values showed a strong dependence on α/β ratio and a considerable scatter for various particle types indicate particle specific behaviour of initial its slope. The surviving curves show a non-linear dose-response suggesting that interaction among DSBs induced by ionizing radiation contribute significantly to the quadratic term of the model. Nonetheless, our simulation results suggest that not only is the model suited for effectively predicting the relative biological effectiveness of the charged particles at low LET and different survival, but also to accuracy in prediction of cell-killing in radiotherapy such as hadrontherapy.