HEPATOMA-CELLS ADAPTED TO PROLIFERATE UNDER NORMALLY LETHAL HYPERTHERMIC STRESS CONDITIONS SHOW RAPID DECAY OF THERMORESISTANCE AND HEAT-SHOCK PROTEIN-SYNTHESIS WHEN RETURNED TO 37-DEGREES-C

H35 hepatoma cultures were adapted to sustained growth at 41.3 degrees C. In these variant cells the 'basic' levels of various heat shock pr oteins (hsps), especially those of hsp60, 70 and 100, are significantl y raised. These cells exhibit a thermoresistance comparable with the i nduced thermotolerance in normal hepatoma cells heat shocked at 42.5 d egrees C for 30 min. However, this resistance of variant cells shows a rapid, exponential decay with a half-time of 2.2 h when the temperatu re is lowered to 37 degrees C, with a concomitant decrease of the synt hesis of hsp60 and 70. Heat shock experiments with variant cells grown at 41.3 degrees C lead to increased thermoresistance and synthesis of hsps when further incubation was performed at the original temperatur e but not at 37 degrees C. In the latter case, only a 3-h delay in the onset of decay of thermoresistance is observed. However, when the var iant cells were incubated at 37 degrees C prior to heat stress normal induction of thermoresistance and hsp synthesis return inversely propo rtional to the progression of thermoresistance decay. Thermoresistant cells thus seem to be valuable tools in the study of the down-regulati on of thermoresistance as well as of hsp synthesis.