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Protection against Heat-induced Cell Killing by Polyols in Vitro¹

Department of Medicine, Veterans Administration Medical Center and University of Arkansas for Medical Sciences, Little Rock, Arkansas [K. J. H.], and Department of Radiology, University of Utah Medical Center, Salt Lake City, Utah [J. W. P., R. H.]

The polyols erythritol and adonitol reduced 45° heat killing in asynchronous Chinese hamster ovary cells. Heat protection by glycerol and erythritol increased with the apparent intracellular concentration, as inferred from cell volume measurements, and the number of hydroxyl groups per alcohol molecule. The nonlinear tetrahydroxy alcohol pentaerythritol did not protect but sensitized to heat killing. On cell survival curves, the reduced cell killing of protected cells was expressed by an increased D₀ for the pentahydroxy alcohol adonitol (0.3 M), whereas equimolar concentrations of glycerol increased primarily the D_q (quasithres-hold dose) with little increase in D₀. The distribution of Chinese hamster ovary cells within the cell cycle was unaffected by the presence of 0.3 M glycerol in the culture medium. However, the polyols erythritol and sorbitol caused a small but significant loss of cells from the heat-resistant G₁ compartment. The cell cycle redistribution with prolonged incubation (6 hr) in polyol-supplemented medium is expected to increase the heat sensitivity of the perturbed cell population; the observed heat protection by polyols suggests that heat resistance in the presence of polyols is not an artifact of an asynchronous cell system. Instead, the data identify a family of heat-protective compounds that may occur naturally in mammalian cells.

¹ This investigation was supported by USPHS grants CA-33405 and CA-33406 awarded by the National Cancer Institute, Department of Health and Human Services. A polyol is defined by the generalized formula CH₂OH (CHOH)_nCH₂OH: glycerol, n = 1; erythritol, n = 2; adonitol, n = 3; sorbitol and its stereoisomers, n = 4.

² To whom requests for reprints should be addressed, at Medical Research Service (151/7), Veterans Administration Medical Center, 300 East Roosevelt Road, Little Rock, Ark. 72206.

Received 8/23/82. Accepted 1/ 3/83.