Thermal radiosensitization and repair inhibition in human melanoma cells: a comparison of survival and DNA double strand breaks.

Human melanoma cells (SK-mel-3) were treated with combinations of radiation and hyperthermia treatment and survival (using the colony forming assay) and DNA double strand breaks (dsb's) (using pulsed field gel electrophoresis) were measured for immediate and delayed plating. The cells were treated in plateau phase, so that delayed plating would result in repair of potentially lethal damage (PLD). Delayed plating showed PLDR for both the survival and the dsb end-point. One hour of heating after irradiation showed a temperature dependent increase in radiosensitization for both the survival endpoint and the dsb endpoint for the temperature range from 42 to 45 degrees C. One hour of heating at 43 degrees C after irradiation resulted in the partial inhibition of PLDR and recovery of dsb's. For heating at 45 degrees C the inhibition of dsb repair was complete. There was good correlation between the survival endpoint and the dsb endpoint for the thermal radiosensitization for both the immediate plating and the PLDR protocols. These data indicate that hyperthermia inhibition of repair of PLD is probably due to the inhibition of dsb rejoining. These correlations were made at the same dose levels for survival and dsb analysis, thus avoiding the potential complications of many earlier studies which used much higher doses for dsb analysis than for survival studies.