Modification of the Heat Response and Thermotolerance by Cycloheximide, Hydroxyurea, and Lucanthone in CHO Cells

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Abstract
Exposure of Chinese hamster ovary [CHO] cells to cycloheximide for 2 h immediately prior to 45.degree. C hyperthermia increased cell survival by a factor of 1.8. The increase in cell survival was independent of the heating time for heat treatments longer than 10 min at 45.degree. C and was similar with cycloheximide concentrations of 1 and 10 .mu.g/ml. Thermotolerance was induced by an initial treatment of 10 min at 45.degree. C (conditioning), developed during a 7-h incubation period at 37.degree. C, and was defined by the hyperthermia dose response with a second 45.degree. C heat treatment. When cycloheximide (1 .mu.g/ml) was added to the medium after heat conditioning and removed prior to the 2nd heat treatment, the degree of thermotolerance was 50% less than that in medium controls. A 3-h exposure to 10 .mu.g/ml cycloheximide at 37.degree. C by itself did not result in the progressive development of thermotolerance which occurs after a conditioning heat treatment. In contrast to the effects of cycloheximide, hydroxyurea (1 mM) and lucanthone (5 .mu.g/ml) showed little effect on the heat sensitivity and the development of thermotolerance after heat conditioning. Although the results can be interpreted that the development of thermotolerance requires the synthesis of new proteins, but not that of DNA and RNA, alternate interpretations are possible based on known cycloheximide effects aside from its primary inhibition of protein synthesis.