The multi-step nature of carcinogenesis and the implications for risk analysis

Purpose: For the purposes of constructing biologically realistic models of radiation cancer risk it is necessary to have detailed knowledge of the post-irradiation mechanisms involved. Methods: This brief review considers selected aspects of DNA damage response, tumour initiation/development, together with attendant factors and provides comment on the implications for cancer risk estimation and some of the uncertainties that remain. Conclusions: It is judged from studies with animal models that, in the main, radiation tumorigenesis proceeds in a conventional multi-step fashion following radiation-induced specific gene losses from single-target stem cells.