Continuous exposure of HeLa cells in culture to elevated temperatures (41–45°) results in cell killing which increases exponentially as the time at the elevated temperature increases linearly. When cells are returned to 37° after an initial thermal dose, cellular sensitivity to subsequent hyperthermic doses is reduced. Cell inactivation rates for cultures previously treated with 44° for either 0.5 or 1 hr followed by incubation at 37° for 2 hr, showed D0's of 1.1 and 1.5 hr, respectively, for subsequent thermal treatments at 44°. Cultures receiving no prior hyperthermic dose had a D0 of 0.5 hr for treatments at 44° for up to 3.5 hr. The viable progeny of cells treated with 44° for 1 hr, however, had the same sensitivity to thermal doses at 44° as did previously unheated cells. These results and others demonstrate that (a) single thermal doses produce a state of thermotolerance in HeLa cells to subsequent hyperthermic doses; (b) the degree of thermotolerance produced is dependent on the magnitude (i.e., temperature and time at the elevated temperature) of the first thermal dose; (c) thermotolerance does not develop at the elevated temperature but requires a return of culture temperatures to 37°; (d) cellular acquisition of thermal tolerance is dependent on cell metabolism, as demonstrated by an inhibition of the effect at 0°; and (e) this effect is a transient phenomenon which is lost as cells divide following the first thermal dose.

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This work was supported by Grants from the American Cancer Society (In-110), the USPHS (IN-3150-80), and the National Cancer Institute (CA 17343, CA 18273).

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