Hyperthermic Radiosensitization of Thermotolerant Chinese Hamster Ovary Cells

Abstract

Synchronous G1 cells were given a priming dose of heat (45.5 degrees C for 15 min) and then heated and irradiated 6-120 h later. Compared to heat radiosensitization for cells irradiated 10 min after the priming heat dose (thermal enhancement ratio, TER of 2.6 for a 10-fold reduction in survival), heat radiosensitization 18-24 h after the priming heat dose was less (i.e., TER of 1.6 for radiation at 24 h compared with heat-radiation at 24 h). A thermotolerance ratio (TTR) at 24 h was calculated to be 2.6/1.6 = 1.6. TERs at 100-fold or 1000-fold reduction in survival and ratios of slopes of radiation survival curves also showed that the cells developed a similar amount of thermotolerance for heat radiosensitization at 18-24 h. Furthermore, since the TER for heat radiosensitization increased with heat killing either from the priming heat dose or the second heat dose in a similar manner for single or fractionated doses, the TER for nonthermotolerant and thermotolerant cells was the same when related to the heat damage (i.e., amount of killing from heat alone). When the radiation response of cells heated and irradiated 6-120 h after the priming heat dose was compared with the response of cells receiving radiation only, changes in TER as a function of time after the initial priming heat dose were shown to involve: recovery of heat damage interacting with the subsequent radiation dose, thermotolerance for heat radiosensitization, and redistribution of cells surviving the first heat dose into radioresistant phases of the cell cycle. In fact, redistribution resulted in a minimal TER at 72 h for heat-radiation compared with radiation alone, instead of at 24 h where maximal thermotolerance for heat killing was observed [P. K. Holahan and W. C. Dewey, Radiat. Res. 106, 111 (1986)]. These observations are discussed relative to clinical considerations and similar results reported from in vivo experiments.

Thermotolerance induced by heat, sodium arsenite, or puromycin: Its inhibition and differences between 43°C and 45°C

“…7A) is due to the differences in the distribution of HSP-70 to the nucleus and nucleolus. This model is consistent with the observation that ARS unlike heat did not induce thermotolerance for heat radiosensitization or loss of DNA polymerase activities (Mivechi and Dewey, 1985;Holahan et al, 1986), namely, alterations associated with the nucleus. For the additional thermotolerance to 45°C induced during treatment a t 43°C after an initial treatment and thermotolerant development phase (Fig.…”

Induction of tolerance to hypothermia and hyperthermia by a common mechanism in mammalian cells

“…Hyperthermia (temperature greater than 41 .O"C) is being used in the treatment of human cancers (Emami and Perez, 1987;Overgaard, 1989); it both kills cells directly and sensitizes cells to conventional radiotherapy (Stewart and Denekamp, 1978;Holahan et al, 1986). One response of cells to hyperthermia is to develop resistance to killing by subsequent hyperthermic exposures, a state of thermal resistance known as thermotolerance (Gerner and Schneider, 1975;Li et al, 1983).…”