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Pressure inhibits thermal killing of Chinese hamster ovary fibroblasts

Abstract

The increasing application of hyperthermia to cancer therapy1–5 has resulted in intensive study of the cellular effects of small temperature elevations (from about 37 to 43 °C). The critical heat target(s) have not been identified, however, findings such as the alterations in membrane morphology, inhibition of potassium transport6 and increased permeability to a variety of substances7,8 implicate the plasma membrane9. Also, there are striking similarities between the response of cells in tissue culture to heat and various membrane fluidizing agents, including anaesthetics and alcohols10–14. An initial exposure of cells to non-lethal doses of heat will trigger development of subsequent resistance to both heat and ethanol, as well as to adriamycin. Similarly, an initial exposure to ethanol will result in subsequent resistance to all three of these agents10–12. A range of anaesthetics and alcohols also act synergistically with heat in cell killing12–14. As the effects of ethanol and many other anaesthetics thought to be membrane active are known to be inhibited by the simultaneous application of elevated pressure15, we suspected that thermal cell killing would also be inhibited by high pressure, as occurs in bacterial systems16. There are marked differences, however, between the response of mammalian cells and bacteria to heat: mammalian cells require only very small elevations in temperatures to effect large changes in survival, and can only grow within a comparatively narrow temperature range. We demonstrate here that pressure does, nevertheless, inhibit thermal killing of mammalian cells.

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Minton, K., Stevenson, M., Kendig, J. et al. Pressure inhibits thermal killing of Chinese hamster ovary fibroblasts. Nature 285, 482–483 (1980). https://doi.org/10.1038/285482a0

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