The effect of hypoxic cell sensitizers at different irradiation dose rates

The effect of 0.1-5 mM misonidazole and SR 2508 on hypoxic V79 cellular survival at acute (498 cGy/min) and low (890 and 933 cGy/h) irradiation dose rates was measured and compared. The experiments were designed to delineate the oxygen mimetic phenomenon and the preincubation effect of these chemicals at these dose rates. Linear regression analysis of the survival data in terms of the linear quadratic model yielded values of alpha and beta. In the absence of drug, the linear coefficient was independent of dose rate, whereas the quadratic term was greatly reduced at low dose rate. At all dose rates, the preincubation effect affected primarily the alpha term, with little influence on beta. In contrast, the oxygen mimetic phenomenon predominantly affected the beta term. Overall, the radiosensitizing ability of these drugs was higher at low dose rate than at acute dose rate.