INDUCTION OF TOLERANCE TO HYPOTHERMIA AND HYPERTHERMIA BY A COMMON MECHANISM IN MAMMALIAN-CELLS

Pretreatment by hypothermic (25-degrees-C) cycling (PHC) of attached exponential-phase V79 Chinese hamster cells by Method 4(24 hr at 25-degrees-C + 1.5 hr at 37-degrees-C + 24 hr at 25-degrees-C + trypsin + 3 hr at 37-degrees-C) or by Method 3 (48 hr at 25-degrees-C + trypsin + 3 hr at 37-degrees-C) make mammalian V79 cells significantly more resistant to 43-degrees-C hyperthermia. There is no significant difference in the 43-degrees-C curves whether Method 3 or 4 is used for pre-exposure. If pre-exposure is at 15 or 10-degrees-C, the resistance to hyperthermia is significantly reduced. PHC by Method 4 significantly increases survival of cells exposed to 5-degrees-C and, to a lesser extent, to 10-degrees-C. The increase in hyper- and hypothermic survival after PHC cannot be accounted for by changes in cell cycle distribution. Heat-shock protein synthesis is not induced by PHC; hence, protection does not result from newly synthesized proteins. When cells are made tolerant to hyperthermia by a pretreatment in 2% DMSO for 24 hr at 37-degrees-C (Method 8), the cells are not more resistant to subsequent exposures to hypothermia, either at 5 or 10-degrees-C. The results imply that there may be two mechanisms of inducing resistance to hyperthermia, only one of which also confers resistance to hypothermia. (C) 1993 Wiley-Liss, Inc.