CHANGES IN HEAT AND RADIATION SENSITIVITY DURING LONG DURATION, MODERATE HYPERTHERMIA IN HELA-S3 CELLS

Step-up heating and thermal radiosensitization were studied at 41.5-degrees-C in HeLa S3 cells under conditions where chronic thermotolerance was not expressed. In spite of this lack of thermotolerance expression, it was possible that thermotolerance to higher temperature treatment had developed. Accordingly, cells were incubated for various times at 41.5-degrees-C, then immediately shifted up to 45-degrees-C, whereupon heating continued for up to 75 min. Thermotolerance to 45-degrees-C heating was observed after 8 hr incubation at 41.5-degrees-C and decayed by 32 hr of continuous incubation at 41.5-degrees-C. When the time of 45-degrees-C treatment was extended to 150 min, the biphasic survival response indicated that chronic thermotolerance was expressed at 45-degrees-C, even though it was not expressed during the 41.5-degrees-C treatment. Thus, chronic thermotolerance can develop under conditions (e.g., at 41.5-degrees-C) where it is not expressed, yet be expressed under other conditions (e.g., during 45-degrees-C exposure). When cultures were x-irradiated after various periods of 41.5-degrees-C treatment, maximum thermal radiosensitization was observed after 4 hr of incubation at 41.5-degrees-C, for which no cell killing was observed due to heat alone. The radiosensitization observed decreased the D0 and D(q) values from about 1.3 Gy to 0.7 Gy and from about 2.0 Gy to 1.0 Gy, respectively. As the duration of the 41.5-degrees-C pre-treatment was extended up to 32 hr, no additional thermal-radiosensitization was observed; all killing due to the heat exposure at 41.5-degrees-C was additive to the radiation killing after the initial induction of thermal radiosensitization. These results demonstrate differences in the thermal and radiation responses of HeLa cells when compared to earlier studies using CHO cells and may be more relevant to the clinical setting.