Interaction of hyperthermia and metabolic inhibitors on the induction of chromosome damage in Chinese hamster ovary cells.

We have examined the chromosomal effects of heating asynchronously growing Chinese hamster ovary (CHO K1) cells in the presence of actinomycin D or cycloheximide. Actinomycin D was found to strongly potentiate the chromosome damaging effects of heat shock, an effect correlated with a strong nonadditive reduction in cell survival. In contrast, cycloheximide treatment reduced heat shock induced chromosome damage and resulted in a significant nonadditive increase in cell survival following heat shock. The different effects of these two inhibitors on chromosomal damage and cell survival are correlated in part with their effects on the rate of DNA synthesis during heat shock. The results suggest that an important aspect of the interaction of heat and metabolic inhibitors involves changes in cell cycle phase distribution of and/or progression through the S phase of the cell cycle induced by drug treatment prior to and during heat shock. The data indicate that the protective effect of cycloheximide in heat shocked cells may involve altered cell cycle progression and/or phase distribution of cells during hyperthermia.