The Cell Cycle Dependence of Thermotolerance: II. CHO Cells Heated at 45.0°C

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Abstract
This report extends previous investigations of the cell cycle dependence of the expression of thermotolerance to include tolerance expressed by Chinese hamster ovary (CHO) cells exposed to 45.0.degree. C hyperthermia. The response of asynchronous cells following exposure at 45.0.degree. C was examined. A maximum in thermotolerance under these conditions was reached .apprx. 12 h after a 15-min exposure to 45.0.degree. C hyperthermia and progressively decreased thereafter. Cells were delayed in S and G2 phase for 24 h, after which time cell growth resumed. The response of CHO cell populations synchronized in G1 or early or late S phase was then characterized. It was observed that the expression of tolerance depended on the position of cells in the cell cycle and was modulated by changes in the sensitivity of cells as they progressed through the cell cycle subsequent to the tolerance induction dose. The variation in the sensitivity of these cells to 45.0.degree. C hyperthermia throughout the cell cycle was measured and substantial changes as cells progressed through S phase were found. Cells in early S phase were the most sensitive to heat at this temperature, and as these cells progressed through S phase, they became progressively more resistant. In addition, G1 cells were delayed for .apprx. 15-18 h by a 15-min, 45.0.degree. C heat pulse, whereas S-phase cells were delayed to a lesser extent. The induction of thermotolerance apparently is relatively non-cell-cycle specific, but the magnitude of expression of tolerance depends on the position of cells in the cell cycle at the time of the subsequent challenge heat dose.

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