HYPERTHERMIA INHIBITS THE REPAIR OF DNA DOUBLE-STRAND BREAKS INDUCED BY IONIZING-RADIATION AS DETERMINED BY PULSED-FIELD GEL-ELECTROPHORESIS

Hyperthermia is known to synergistically interact with X-rays to kill cells. We have used pulsed-field gel electrophoresis to investigate the effects of hyperthermia on cell survival and on repair of radiation-induced DNA double-strand breaks (dsbs). Combining hyperthermia (43-degrees-C, 45 min) with radiation (7.5 Gy) resulted in a complete inhibition of dsb repair and a surviving fraction of 0.9%. Cells treated with hyperthermia alone resulted in a 55 % cell survival with no increase in dsb levels over background. Cells treated with 7.5 Gy alone demonstrated 11% survival and exponential dsb repair. Dsb repair was equally inhibited by hyperthermia whether administered immediately before or after the radiation. We compared the rejoining of dsbs resulting from 7.5 Gy at 37 and 43-degrees-C to determine whether dsbs were being repaired during hyperthermia. While repair occurred at 37-degrees-C, no dsbs were repaired at 43-degrees-C. Our results indicate that hyperthermia completely inhibits dsb repair.