A transient thermotolerant survival response produced by single thermal doses in HeLa cells

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