Modification of the Thermal Response by D 2 O: II. Thermotolerance and the Specific Inhibition of Development

Abstract

In a companion paper it was shown that D/sub 2/O protects cells against the lethal effects of heat and that D/sub 2/O interfers with the induction of thermotolerance. In this paper we investigate the latter phenomenon with particular reference to an operational model of thermotolerance. Plateau-phase Chinese hamster ovary cells (HA-1) were treated at elevated temperatures permissive for the development of thermotolerance (40-42.5/sup 0/C) in media prepared with H/sub 2/O or D/sub 2/O. Cells were given a more lethal dose of heat (45/sup 0/C/45 min with surviving fraction approx. =10/sup -4/) to assess the degree of thermotolerance. Cells pretreated in H/sub 2/O media expressed a two to three log increase in survival, while thermotolerance was effectively suppressed in cells pretreated in D/sub 2/O. However, cells treated in D/sub 2/O media for 4 hr at 42/sup 0/C, then permitted a 37/sup 0/C incubation period in H/sub 2/O media, rapidly recovered their thermotolerance. Interpreting results within the framework of a three-component model of thermotolerance (trigger, development, decay), we suggest the following: (1) D/sub 2/O inhibits the development component of tolerance; (2) the effect of D/sub 2/O on the trigger component is such that the cells behave as if they were treated atmore » a temperature lower by 2/sup 0/C in H/sub 2/O media; (3) the protection afforded by D/sub 2/O is mechanistically different from that of thermotolerance, at least in the sense that they augment each other.« less