Modification of radiation-induced damage by hyperthermia--role of repair processes

The role of repair inhibition in hyperthermic sensitization has been investigated by carrying out interaction studies (non-lethal heat plus radiation) using three radiosensitive mutant strains rad 9-4, rad 51, rad 52 of diploid yeast. The radiosensitization observed in these mutants is compared with that obtained in a wild type strain X2180. Stationary phase cells were heat treated at 51 degrees C for 30 min and log-phase cells at 49 degrees C for 5 min such that the heat treatment per se was non-lethal. Thermal enhancement ratios (TER) were calculated as the ratio of D0 values as well as D10 values, for radiation alone and for combination of heat and radiation. In stationary phase cells TER values ranged from 1.25 to 2 in different strains. There was no significant difference in the degree of sensitization in wild type and mutant strains. However in log-phase cells TER calculated as the ratio of D10 values was 1.84 for wild type strain; whereas the same was 1.2, 1.18 and 1.50 for rad 9-4, rad 51 and rad 52 strains. TER value obtained from ratio of D0 values was also significantly higher for wild type cells in log-phase cultures. These results suggest that the radiosensitization by heat occurs prominently in radioresistant log-phase cells and reflects as a reduction in the shoulder width of survival response curves. Prompt sensitization as seen by the increase in slope of survival curve also contributes to the TER. Inhibition of recovery from sublethal damage by heat appears to be an important mechanism of radiosensitization in log-phase cells.(ABSTRACT TRUNCATED AT 250 WORDS)