Detailed analysis of the cell-inactivation mechanism by accelerated protons and light ions

Published survival data for V79 cells irradiated by monoenergetic protons, helium-3, carbon, and oxygen ions and for CHO cells irradiated by carbon ions have been analyzed using the probabilistic two-stage model of cell inactivation. Three different classes of DNA damages formed by traversing particles have been distinguished, namely severe single-track damages which might lead to cell inactivation directly, less severe damages where cell inactivation is caused by their combinations, and damages of negligible severity that can be repaired easily. Probabilities of single ions to form these damages have been assessed in dependence on their linear energy transfer (LET) values. Damage induction probabilities increase with atomic number and LET. While combined damages play crucial role at lower LET values, single-track damages dominate in high-LET regions. The yields of single-track lethal damages for protons have been compared with the Monte Carlo estimates of complex DNA lesions, indicating that lethal events correlate well with complex DNA double-strand breaks. The decrease in the single-track damage probability for protons of LET above approx. 30 keV/$\mu$m, suggested by limited experimental evidence, is discussed, together with the consequent differences in the mechanisms of biological effects between protons and heavier ions. Applications of the results in hadrontherapy treatment planning are outlined.Comment: submitted to Physics in Medicine and Biolog