Interaction of hyperthermia and radiation in CHO cells: recovery kinetics.

The sensitivity to hyperthermic damage (450C + 0.050) and the interaction of hyperthermic damage with radiation damage was determined in Chinese hamster ovary (CHO) fibroblasts in monolayer culture. The survival curve for asynchronous cells heated at 450C was exponential with a shoulder (Do = 3.6 min, D, = 7.5 min, n = 7.3). Fractionation of two equal heat treatments each of 17.5 min indicated that cell survival was maximally enhanced at a fractionation interval of 12 hr to a survival ratio of approximately 400. Of this, a factor of 60 was due to induction of thermotolerance in terms of an increased Do. Recovery of the capacity to accumulate sublethal damage (return of extrapolation number to 7.3) was complete and occurred within the first 4 hr. By 72 hr the Do returned to normal although the D, persisted at 20 min at 45?C. Heating (17.5 min at 450C) followed immediately by radiation (450 rad) or radiation followed immediately by heating did not produce significantly different survival values. Hyperthermia reduced the Do of the radiation-survival curve by a factor of 1.9 and increased the extrapolation number by a factor of 3. The D, remained unchanged. For intervals up to 48 hr, prior hyperthermia increased the extrapolation number and D, of the radiation-survival curve to approximately 1000 and 650 rad, respectively. However, the Do remained unchanged at approximately 83 rad over the entire interval of 0-72 hr. For the sequence of radiation followed by hyperthermia, the D, of the hyperthermiasurvival curve was reduced to 2.9 min at 450C by simultaneous irradiation but returned to near-normal values after a fractionation interval of 2 hr. The Do of the hyperthermiasurvival curve was unaffected by prior irradiation. Hyperthermia decreased the slope and widened the shoulder of the radiation-survival curve while prior irradiation only affected the shoulder of the subsequent hyperthermiasurvival curve. The recovery kinetics and extensive resistance of heated cells to a second heat dose are difficult to explain solely by the rate process theory of protein denaturation. However, denaturation of membrane or chromatin proteins associated with intracellular recovery mechanisms may account for the effects of hyperthermia alone on cell survival and its modification of the radiation response.

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