DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

• Presented a mechanistic model of DSB repair in early S and G1 cell cycle.
• The model considers the repair of simple, complex, and DSB in heterochromatin.
• Tested hypothesis the kinetics of DSB repair is a function of complexity of DSBs.
• Applied the model to DSB induced by protons and ions and compared with experiments.
• The model is able predict repair kinetics of DSBs induced by different radiations.

The purpose of this work is to test the hypothesis that kinetics of double strand breaks (DSB) repair is governed by complexity of DSB. To test the hypothesis we used our recent published mechanistic mathematical model of DSB repair for DSB induced by selected protons, deuterons, and helium ions of different energies representing radiations of different qualities. In light of recent advances in experimental and computational techniques, the most appropriate method to study cellular responses in radiation therapy, and exposures to low doses of ionizing radiations is using mechanistic approaches. To this end, we proposed a ‘bottom–up’ approach to study cellular response that starts with the DNA damage. Monte Carlo track structure method was employed to simulate initial damage induced in the genomic DNA by direct and indirect effects. Among the different types of DNA damage, DSB are known to be induced in simple and complex forms. The DSB repair model in G1 and early S phases of the cell cycle was employed to calculate the repair kinetics. The model considers the repair of simple and complex DSB, and the DSB produced in the heterochromatin. The inverse sampling method was used to calculate the repair kinetics for each individual DSB. The overall repair kinetics for 500 DSB induced by single tracks of the radiation under test were compared with experimental results. The results show that the model is capable of predicting the repair kinetics for the DSB induced by radiations of different qualities within an accepted range of uncertainty.