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Studies on the Quantitative Biology of Hyperthermic Killing of HeLa Cells¹

McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

The quantitative biology of hyperthermic killing of HeLa cells was studied. Plots of cell survival versus doses of hyperthermia did not show first-order kinetics. The rate of HeLa cell killing shows a striking temperature-dependent relationship in the 41.0–43.0° temperature range. There is a delay of approximately 1 day in the division of cells heated to 42.0°, after which time some cells resume normal growth, whereas others divide at least once before death. Cells selected for their capacity to survive prolonged periods of hyperthermia are killed at approximately the same rate during subsequent heat treatments as cells that had not been heated previously. Hyperthermic cell killing is reduced in cells that are heated in the presence of certain compounds that are inhibitors of DNA and protein synthesis. Fractionated dose experiments indicate that cells recover from sublethal hyperthermic damage. Furthermore, hyperthermic killing is at least a two-step process, and cells are capable of recovery from potentially lethal damage, particularly in the presence of cycloheximide and high levels of thymidine.

¹ This work was supported in part by Grants CA-07175 and CRTY-5002 from the National Cancer Institute, NIH.

² American Cancer Society Professor of Oncology.

Received 9/13/72. Accepted 11/ 8/72.

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