Parameters of linear-quadratic radiation dose-effect relationships: dependence on LET and mechanisms of reproductive cell death

An analysis of mammalian cell radiation-dose survival curves, based on the linear-quadratic formalism, is shown to yield insights in the various components of damage that contribute to cell reproductive death. RBE-LET relationships of single-track lethal damage, sublethal damage, potentially lethal damage and DNA double-strand breaks are compared. Single-track lethal damage is derived to be composed of two components: (1) damage that remains unrepaired in an interval between irradiation and assay for proliferative capacity, with a very strong dependence on LET, and (2) potentially lethal damage that is only weakly dependent on LET, similar to sublethal damage and DNA double-strand breaks. The results of this analysis lead to new interpretations of published experimental results and to suggestions for applications in radiotherapy.