Survival Curves with Shoulders: Damage Interaction, Unsaturated but Dose-Dependent Rejoining Kinetics or Inducible Repair of DNA Double-Strand Breaks?

Double-strand breaks (DSBs) are considered as critical lesions for radiation-induced cell killing. Two processes, identified by the rejoining kinetics of DNA DSBs induced in yeast at radiation doses which are also applied in survival studies, can lead to survival curves with shoulders: firstly, "DSB interaction" when repair time is unrestricted, and secondly, a biphasic and unsaturated DSB rejoining, where the fractions of the two rejoining components are dose-dependent and repair time is restricted. Thus the unsaturated rejoining kinetics of DSBs is not in contradiction to the observation of survival curves with shoulders. While these two mechanisms are derived from studies on cells kept under nongrowth conditions during postirradiation incubation, experiments are reviewed which were designed to study inducibility of DSB rejoining. Some of these studies suggest that rejoining of DSBs under growth conditions may include an inducible process.