THE EFFECT OF RADIOSENSITIZERS ON THE SURVIVAL RESPONSE OF HYPOXIC MAMMALIAN-CELLS - THE LOW X-RAY DOSE REGION, HYPERSENSITIVITY AND INDUCED RADIORESISTANCE

It has been shown previously that the extent of chemical modification of the hypoxic radiation response is dependent on dose. Some types of sensitizer are more effective at low doses (to 4 Gy) than at higher do ses. Since such drugs are possible adjuvants to radiotherapy, the mech anisms responsible for the variable response at clinical doses are of interest. Existing reports on sensitization at low doses are summarize d, and the effects of cisplatin and buthionine sulfoximine on the purp orted induced response to radiation in hypoxic cells are presented. Ci splatin at a low, nontoxic concentration (1 mu M) appears to abolish t he increased radioresistant portion of the survival response. A role f or high-mobility-group protein binding by platinum drugs is hypothesiz ed to explain their interaction with radiation, and conversely, it is suggested that the heretofore unexplained different behavior of certai n hypoxic sensitizers at low doses could be, at least in part, an effe ct on the induction of resistance.