Mechanisms of acquired resistance to acute heat shock in cultured mammalian cells

A clonal strain of mammalian cells with increased resistance to acute heat shock at 46° was compared with the heat-sensitive parental line from which it was derived for possible differences that might account for this acquired resistance. Studies on synchronized populations of the two cell strains did not reveal any differential heat sensitivities in the various parts of the cell cycle (G₁, S, G₂) within either the sensitive or resistant populations. During thermal stress both cell types exhibited marked inhibition of ability to incorporate isotopically labeled precursors into macromolecular RNA, DNA, and protein. However, significant differences were observed between the sensitive and resistant cells in the amount of leakage of materials from the two cell types during heat stress and in their relative rates of recovery after stress. Sensitive cells pre-labeled with ³H-uridine released considerably more acid-soluble (cold, 5% TCA) label-containing materials during heat stress than did pre-labeled resistant cells. This differential release of uridine-containing materials was not paralleled by a generalized differential leakiness to other compounds. In addition, the resistant cells were found to regain the capacity to synthesize vital macromolecules sooner, and at initially faster rates, than the sensitive cells after stress. These results suggest that permeability changes causing decreased leakage of uridine-containing materials during heat stress combined with accelerated rates of recovery of synthesis of essential macromolecules after stress may be important cellular mechanisms in resistance to heat shock.