Cell-cycle sensitivity, recovery from radiation damage and a new paradigm for risk assessment

Tikvah Alper's interest in science was broad, from scrapie to mammalian cells and cancer. Much of her own work focused on cell lethality, like that of many other radiobiologists, but this was natural because of the simplicity of the endpoint cell survival and its relevance to cancer therapy. Tikvah had broader interests, however, that included the effects of radiation on living systems in general like the induction of cancer and the cellular and molecular processes contributing to it. In this essay, some ideas are developed that lie in the mainstream of her interests. Starting with functional measures of the recovery or repair from radiation damage, a role for repair is illustrated in connection with mutagenesis and neoplastic transformation both discussed in the context of radiation-induced cancer. These topics are central to a model explaining the anomalous enhanced neoplastic transformation and cancer observed when low doses of a high-LET radiation are protracted in time. Under particular circumstances, the formalism of the model predicts application to protracted low-LET exposures as in the instance of repair-deficient target cells and sporadic breast cancer. The latter discussion leads to the proposal that the paradigm in current use for evaluating cancer risk should be broadened: from a simple dose-effect relation to one that includes cell kinetics (during protracted exposures), cell-cycle dependencies, and the influence of cellular repair or the lack thereof.