Explanation of protective effects of low doses of γ-radiation with a mechanistic radiobiological model

Purpose: To test whether data that show protective effects of low doses against spontaneous neoplastic transformation of C3H 10T1/2 cells can be explained with a biomathematical model that includes radioprotective mechanisms. To link important features of the model to known biological processes. Materials and methods: The model simulates double-strained break formation in transcriptionally active and in bulk DMA, translocation of DNA segments, and the fixation of damage at mitosis; promotion is also included. The model equations were solved numerically using a stiff solver. Results: The data were successfully simulated by the model: cell transformation-reducing effects of low doses of gamma-radiation delivered at low dose-rates are explained by radiation-inducible DNA repair and enzymatic scavenging. Conclusions: The model successfully simulates experimental data. The highly nonlinear features of the data point to a nonlinear dose effect relationship at low doses and indicate that linear extrapolation from moderate (or high) to low doses and dose-rates may not be justified for in vitro studies of the cell line under consideration.