Modelling of Cellular Survival Following Radiation-Induced DNA Double-Strand Breaks

Abstract

A mechanistic model of cellular survival following radiation-induced DNA double-strand breaks (DSBs) was proposed in this study. DSBs were assumed as the initial lesions in the DNA of the cell nucleus induced by ionizing radiation. The non-homologous end-joining (NHEJ) pathway was considered as the domain pathway of DSB repair in mammalian cells. The model was proposed to predict the relationship between radiation-induced DSBs in nucleus and probability of cell survival, which was quantitatively described by two input parameters and six fitting parameters. One input parameter was the average number of primary particles which caused DSB, the other input parameter was the average number of DSBs yielded by each primary particle that caused DSB. The fitting parameters were used to describe the biological characteristics of the irradiated cells. By determining the fitting parameters of the model with experimental data, the model is able to estimate surviving fractions for the same type of cells exposed to particles with different physical parameters. The model further revealed the mechanism of cell death induced by the DSB effect. Relative biological effectiveness (RBE) of charged particles at different survival could be calculated with the model, which would provide reference for clinical treatment.