INTERPRETATION OF INVERSE DOSE-RATE EFFECTS FOR MUTAGENESIS BY SPARSELY IONIZING-RADIATION

An inverse dose-rate effect has sometimes been observed for mutagenesi s in cells exposed to gamma-rays. We model such data quantitatively wi th the key assumption that the effect is caused in cycling cells by co rrelated variations in sensitivity across the cell cycle, for both mut ation and killing. We quantify this approach using the LQR (linear-qua dratic + resensitization) formalism, which describes the response to r adiation of a heterogeneous cell population. This model is applied to an exponentially growing population. We compare its predictions with d ose- and dose-rate dependent mutation data and show that it can well f it the observed inverse dose-rate effect, as well as providing an expl anation of why inverse dose-rate effects have been seen in some experi ments, but not in others. The actual values of the model parameters em erging from the analysis are reasonable in magnitude, based on their b iological interpretations. We conclude that the LQR model can quantify cell-cycle redistribution effects without over-parameterization, and that tile data favour a correlation explanation of inverse dose-rate e ffects for mutagenesis by low-LET radiation. It is less clear that thi s explanation is appropriate to high-LET radiation-induced oncogenic t ransformation, although all potential explanations of inverse dose-rat e effects predict that, at appropriately low doses, no dose-rate effec ts of any kind are expected.