A generalized concept for cell killing by heat. Effect of chronically induced thermotolerance.

Chronic thermotolerance was induced in Chinese hamster ovary (CHO) cells by pretreatment at 40 degrees C for various times ranging from 15 min to 16 h. The thermotolerant cells were either exposed to single heat treatments at 43 degrees C or subjected to step-down heating consisting of a priming treatment at 43 degrees C for 90 min followed immediately by a graded test treatment at 40 degrees C. Data evaluation using a mathematical model published previously (H. Jung, Radiat. Res. 106, 56-72, 1986) showed that the rate constants p for the production of nonlethal lesions at 43 and 40 degrees C decreased by a factor of 20 with the duration of the thermotolerance-inducing pretreatment at 40 degrees C and approached exponentially (half-time 1.24 +/- 0.11 h) a minimum value. By contrast, the rate constants c for the conversion of nonlethal lesions into lethal events were not altered by the induction of thermotolerance; this applied to both c (43 degrees C) and c (40 degrees C). After transferring thermotolerant cells (pretreatment at 40 degrees C for 3 h) to 37 degrees C, the rate constants p increased exponentially with time (doubling time 25 +/- 5 h). Similar kinetics for the development and decay of chronic thermotolerance was shown to be applicable also to extended heating at 40 degrees C and to various data from the literature.