Computational modeling and a Geant4-DNA study of the rejoining of direct and indirect DNA damage induced by low energy electrons and carbon ions.

PURPOSE

DNA double-strand breaks (DSBs) created by ionizing radiations are considered as the most detrimental lesion, which could result in the cell death or sterilization. As the empirical evidence gathered from the cellular and molecular radiation biology has demonstrated significant correlations between the initial and lasting levels of DSBs, gaining knowledge into the DSB repair mechanisms proves vital. Much effort has been invested into understanding the mechanisms triggering the repair and processes engaged after irradiation of cells. Given a mechanistic model, we performed - to our knowledge - the first Monte Carlo study of the expected repair kinetics of carbon ions and electrons using on the one hand Geant4-DNA simulations of electrons for benchmarking purposes and on the other hand quantifying the influence of direct and indirect damage. Our objective was to calculate the DSB repair rates using a repair mechanism for G and early S phases of the cell cycle in conjunction with simulations of the DNA damage.

MATERIALS AND METHODS

Based on Geant4-DNA simulations of DSB damage caused by electrons and carbon ions - using a B-DNA model and a water sphere of 3 m radius resembling the mean size of human cells - we derived the kinetics of various biochemical repair processes.

RESULTS

The overall repair times of carbon ions increased with the DSB complexity. Comparison of the DSB complexity (DSB) and repair times as a function of carbon-ion energy suggested that the repair time of no specific fraction of DSBs could solely be explained as a function of DSB complexity.

CONCLUSION

Analysis of the carbon-ion repair kinetics indicated that, given a fraction of DSBs, decreasing the energy would result in an increase of the repair time. The disagreements of the calculated and experimental repair kinetics for electrons could, among others, be due to larger damage complexity predicted by simulations or created actually by electrons of comparable energies to x-rays. They are also due to the employed repair mechanisms, which introduce no inherent dependence on the radiation type but make direct use of the simulated DSBs.