The Cell Cycle Dependence of Thermotolerance: I. CHO Cells Heated at 42°C

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Abstract
The dependence was examined of heat killing [hyperthermia, an anticancer modality] and thermotolerance on the position and progression of Chinese hamster ovary (CHO) cells in the cell cycle. Cell cycle perturbations and survival were measured of asynchronous and synchronized G1-, S- and G2-phase cells resulting from continuous heating at 42.0.degree. C for up to 80 h. Thermotolerance under these conditions was transient in nature, was dependent on the position of cells in the cell cycle, and occurred concurrently with a heat-induced delay of progression of G1- and G2-phase cells. When G1 cells were heated, survival decresed to 25% after 4 h, at which time the thermotolerance was expressed. For G2 cells survival decreased initially at the same rate (T0 .simeq. 3 h) but thermotolerance was not expressed until approximately 12 h, at which time the survival was 4%. The rate of decrease in survival was much more rapid for cells heated in mid-S phase (T0 .simeq. 0.5 h), and these cells did not express thermotolerance at a measurable level. Concurrent with the expression of thermotolerance, the progression of cells heated in G1 and G2 was delayed. Following the expression of tolerance, progression resumed at a rate approximately equal to the rate of decrease in survival of the G1 population. Cells heated in mid-S phase continued to progress through the cell cycle until they reached G2, where they were also delayed.

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