Sensitization of rat 9L gliosarcoma cells to low dose rate irradiation by long duration 41 degrees C hyperthermia

Modification of survival by long duration, 41 degrees C hyperthermia in combination with low dose rate radiation (0.5 Gy/h) was determined in rat 9L gliosarcoma cells. Cells were exposed to radiation in a manner that simulated continuous irradiation at a dose rate relevant to clinical brachytherapy. High dose rate X-irradiation was fractionated in 1.0-Gy fractions at 2-h intervals (FLDRI). Previous studies had demonstrated that 9L cells exposed to FLDRI with these parameters have survival characteristics that are equivalent to continuous low dose rate irradiation. Cells exposed to 41 degrees C throughout FLDRI were sensitized significantly (thermal enhancement ratio of 2.07) compared with cells irradiated at 37 degrees C. Incubation for 24 h at 41 degrees C before and/or after FLDRI at either 37 degrees C or 41 degrees C did not increase the slope of the radiation survival curves but did reduce the shoulder. Similarly, heating at 43 degrees C for 30 or 60 min before and/or after irradiation at 0.5 Gy/h also did not enhance cell sensitivity. Survival of cells after irradiation at high dose rate (60 Gy/h) was independent of the temperature during irradiation. Preheat at 41 degrees C for 24 h did not sensitize cells to high dose rate irradiation by increasing the slope of the survival curve, although a loss of shoulder was observed. Sensitization of cells heated at 43 degrees C for 30 or 60 min before high dose rate irradiation was expressed as classical slope modification. Our results demonstrate that 41 degrees C heating during FLDRI greatly sensitizes cells to radiation-induced killing for exposure durations up to 36 h. Heating 9L cells at 41 degrees C or 43 degrees C adjacent to FLDRI at 0.5 Gy/h resulted in no additional enhancement of terminal sensitivity, although shoulder modification was observed. The sensitization by simultaneous heating described above occurred even though thermotolerance developed during extended incubation at 41 degrees C. These in vitro data demonstrate that simultaneous protracted heating at modest temperatures could greatly enhance the cytotoxic effects of low dose rate interstitial irradiation and could be of significance in clinical application.