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

A detailed study of the biological effects of diverse quality radiations, addressing their biophysical interpretation, is presented. 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 analysed using the probabilistic two-stage model of cell inactivation. Three different classes of DNA damage formed by traversing particles have been distinguished, namely severe single-track lesions which might lead to cell inactivation directly, less severe lesions where cell inactivation is caused by their combinations and lesions of negligible severity that can be repaired easily. Probabilities of single ions forming these lesions have been assessed in dependence on their linear energy transfer (LET) values. Damage induction probabilities increase with atomic number and LET. While combined lesions play a crucial role at lower LET values, single-track damage dominates in high-LET regions. The yields of single-track lethal lesions for protons have been compared with 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 approximately 30 keV microm(-1), 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.