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°C for various times ranging from 15 min to 16 h. The thermotolerant cells were either exposed to single heat treatments at 43°C or subjected to step-down heating consisting of a priming treatment at 43°C for 90 min followed immediately by a graded test treatment at 40°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°C decreased by a factor of 20 with the duration of the thermotolerance-inducing pretreatment at 40°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°C) and c(40°C). After transferring thermotolerant cells (pretreatment at 40°C for 3 h) to 37°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°C and to various data from the literature.