A generalized concept for cell killing by heat. Effect of acutely induced thermotolerance and decay of thermosensitization.
Acute thermotolerance was induced in Chinese hamster ovary cells by heating at 43 degrees C for 45 min followed by incubation at 37 degrees C for up to 85 h. The degree of thermotolerance induced was quantified by a second heat exposure at 43 degrees C. To study the interaction of thermotolerance and thermosensitization, thermotolerant cells (43 degrees C/45 min-->37 degrees C/10 h) were subjected to step-down heating consisting of a priming heat treatment at 43 degrees C for 45 to 300 min followed immediately by a graded test treatment at 40 degrees C. Decay of thermosensitization was assayed by separating the priming treatment at 43 degrees C for 45 or 60 min and the test treatment at 40 degrees C by incubation at 37 degrees C for up to 24 h. The experimental data were analyzed by using a mathematical model published previously (H. Jung, Radiat. Res. 106, 56-72, 1986). According to this model, cell killing by heat is a two-step process. In a first step, heating produces nonlethal lesions at a rate p which, in a second step, are converted into lethal events at a rate c. Both rates were shown to depend on temperature. Data analysis, which was performed under the assumption that the rate constant c(T) is not altered by acute thermotolerance, showed that the rate constant p(43 degrees C) decreased exponentially (half-time 1.08 +/- 0.15 h) with increasing thermotolerance development, i.e., with increasing duration of the incubation interval at 37 degrees C. The rate p(43 degrees C) approached a minimum value by 14 +/- 3 h, where it was lower by a factor of 30 compared to normally sensitive cells. For incubation times at 37 degrees C exceeding 14 h, p(43 degrees C) increased exponentially with a doubling time of 13.9 +/- 0.9 h and approached the control level by 85 h. Decay of thermosensitization was quantified by calculating the number of nonlethal lesions from the data recorded for the sequences 43 degrees C-->37 degrees C-->43 degrees C and 43 degrees C-->37 degrees C-->40 degrees C. With increasing incubation interval at 37 degrees C, the number of nonlethal lesions induced per cell by a priming heat shock at 43 degrees C for 45 min remained constant for about 1.5 h and then decreased exponentially with a half-time of 2.0 +/- 0.5 h. Thus the two processes that occur simultaneously after a heat shock at 43 degrees C for 45 min, i.e., development of acute thermotolerance and decay of thermosensitization, proceed with different kinetics as could be separated by applying the model.
Jung
H
H
Institute of Biophysics and Radiobiology, University of Hamburg, Germany.
D000818:Animals; D016466:CHO Cells; D016923:Cell Death; D006224:Cricetinae; D006358:Hot Temperature; D066298:In Vitro Techniques; D008954:Models, Biological; D013696:Temperature; D013997:Time Factors