UvA-DARE (Digital Academic Repository) Parameters of linear-quadratic radiation dose-effect relationships: dependence on LET and mechanisms of reproductive cell death

An analysis of mammalian cell radiation ± dose surIn studies concerning mechanisms that determine vival curves, based on the linear ± quadratic formalism, is shown radiosensitivities of mammalian cells, three di å erent to yield insights in the various components of damage that approaches can be distinguished which complement contribute to cell reproductive death . R B E ± LET relationships of each other and together eventually should result in single-track letha l damage, sublethal damage, potentially letha l a complete description of the processes of induction damage and DNA double-strand breaks are compared. Singletrack letha l damage is derived to be composed of two componand expression of cellular damage (Barendsen 1990). ents : (1) damage that remains unrepaired in an interval between In the biophysical approach dose± e å ect relations irradiation and assay for proliferative capacity, with a very strong are studied with respect to their dependence on two dependence on LET, and (2) potentially letha l damage that is major physical factors: (1) the distribution of dose in only weakly dependent on LET, sim ilar to sublethal damage and time and (2) the spatial distribution of energy deposDNA double-strand breaks. The results of this analysis lead to new interpretation s of published experimenta l results and to ition along the tracks of ionizing particles in cells. suggestions for applications in radiotherapy. Studies of the in ̄ uence of dose fractionation and dose-rate have shown the importance of the contribution of sublethal damage (SLD) to cell lethality and