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Thermotolerance as a Possible Cause of the Critical Temperature at 43° in Mammalian Cells¹

Departments of Physics and Biology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1

Most mammalian cell lines appear to have a critical temperature near 43° in their response to hyperthermia. This critical temperature is usually defined as the temperature at which a break occurs in an Arrhenius plot of the rate of cell killing. Below this temperature, thermotolerance (the appearance of a more heat-resistant subpopulation during the survival curve) is also observed. This critical temperature may indicate a real change in the cellular response to heat or may be due to thermotolerance. For example, an apparent (measured) increase in the D₀ relative to the actual D₀ of the normal or sensitive population can be due to the following: (a) the presence of a normal (or sensitive) subpopulation and a thermotolerant subpopulation; (b) the induction with time of thermotolerance at a hyperthermic temperature in a defined subpopulation; or (c) the induction of thermotolerance with time in the surviving population. Thus, the critical temperature at 43° may be an artifact due to this increase in the measured D₀ instead of being due to a change in the mode of inactivation of cells at that temperature. If this is true, the 43° critical temperature should be considered as the maximum temperature at which thermotolerance can be induced and not as an inflection point indicating two modes of cell killing.

¹ Supported by the Natural Sciences and Engineering Research Council of Canada.

Received 3/10/80. Accepted 9/ 9/80.