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Influence of Drugs and Synchrony on the Hyperthermic Killing of HeLa Cells¹

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

Hyperthermic killing of HeLa cells is cell-cycle phase dependent. Cells were killed to the greatest extent when heated for 1 to 2 hr at 42.0° during late-S or early-G₂ phases, and there was up to a 7-fold increase in viability when cells were heated at other phases of the cell cycle. Hyperthermia produces an inhibition of the incorporation of thymidine-³H, uridine-³H, and leucine-³H into heated cells. Hyperthermic inhibition of DNA and protein synthesis may represent a cellular protective mechanism against hyperthermic killing, since cell viability is higher when cells are heated in the presence of compounds that inhibit these processes. Conversely, hyperthermic inhibition of RNA synthesis appears to be causally related to hyperthermic cell killing, since killing is enhanced when cells are heated in the presence of compounds that inhibit RNA synthesis during hyperthermia.

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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