Hyperthermia and inhibition of the repair of X-ray induced DNA double-strand breaks

The authors have investigated the molecular basis for synergistic cell killing between hyperthermia and X-rays and have investigated whether this interaction results from a hyperthermia inhibition of repair of X-ray induced DNA double-strand breaks (DSB). Mouse L1210 cells were used to study the synergistic effects of combined hyperthermia followed by X-rays. They investigated cell killing induced by hyperthermia and 3-Gy X-rays. A thermal dose of 410C, 2 hr resulted in no synergism (synergism factor=1.13), 430C, 15 min resulted in the greatest synergism (S.F.=2.87) and 45.50C, 5 min showed less synergism (S.F.=2.23). DNA DSB were measured by neutral elution technique. With a dose of 50-GY, a rapid repair of DNA DSB was evident (T1/2=21 min) followed by a slow repair component (T1/2=96 min). Prior heat treatment at 410C, 2 hr did not alter the repair rate after 50-Gy. Prior heat treatment at 430C, 15 min inhibited the rapid repair (T1/2=42 min) and the slow repair (T1/2=396 min) components. Prior heat at 45.50C, 5 min did not alter the initial rapid repair. Therefore, the authors have found a potential correlation between hyperthermic inhibition of the initial fast repair of DNA DSB and the ability of hyperthermia to cause synergistic cell killing with ionizing radiation