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Cellular Glutathione, Thermal Sensitivity, and Thermotolerance in Chinese Hamster Fibroblasts and Their Heat-resistant Variants¹

Department of Radiation Oncology, Radiation Oncology Research Laboratory, CED-200, University of California, San Francisco, California 94143

HA-1 Chinese hamster fibroblasts and two heat-resistant variants, designated 2242 and 3012, have been investigated to determine the role that glutathione (GSH) plays in intrinsic cellular resistance to heat and in the development of thermotolerance. The constitutive levels of GSH did not correlate with intrinsic heat sensitivities, but depletion of GSH sensitized all three cell lines to thermal stress. After heating (43.5°C/2 h), surviving fractions were 1 x 10^-3, 1 x 10^-2, and 8 x 10^-3 for HA-1, 2242, and 3012 cells, respectively. Depletion of cellular GSH with L-buthionine-S,R-sulfoximine to less than 10% of control values sensitized such that the thermal responses of these three cell lines were nearly indistinguishable at 43.5°C. Surviving fractions were 2 x 10^-4, 1 x 10^-4, and 1 x 10^-4 for L-buthionine-S,R-sulfoximine-treated HA-1, 2242, and 3012 cells, respectively, following heating at 43.5°C for 2 h.

The development of thermotolerance in HA-1 cells following heat shock (45°C/15 min) was unaffected by the inhibition of GSH synthesis. On the other hand, when GSH levels were maintained at extremely low levels, the development of thermotolerance was inhibited. In addition, following heat shock, cellular GSH was decreased and remained below control levels during the development of thermotolerance.

¹ Supported by American Cancer Society Grant PDT-225 and USPHS Grants CA 31397 and CA 38847.

² To whom requests for reprints should be addressed.

Received 9/ 5/85. Revised 1/ 7/86. Accepted 1/ 7/86.