Thermotolerance as a possible cause of the critical temperature at 43 degrees in mammalian cells.

Most mammalian cell lines appear to have a critical temperature near 43 degrees 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 Do relative to the actual Do 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 degrees may be an artifact due to this increase in the measured Do instead of being due to a change in the mode of inactivation of cells at that temperature. If this is true, the 43 degrees critical temperature should be considered as the maximum temperature at which thermotolerance can be induced and not as an infection point indicating two modes of cell killing.