Sulfhydryl Compounds as Thermosensitizers

Abstract

The cytotoxic effects of a number of widely used chemotherapeutic agents have been reported to be enhanced by heat (Hahn 1979; Hahn and Li 1982). The exact mechanism of this enhancement is not fully understood and might differ with the various compounds. Thermosensitization by sulfhydryl compounds in vitro has been observed by Kapp and Hahn (1979). We have previously reported that the thermosensitizing effect at 44° C and 43° C of sulfhydryl compounds like cysteamine can be modified by catalase (Issels et al. 1984). The enhancement of thiol cytotoxicity by hyperthermia was found to be due to the generation of activated oxygen species during the autoxidation of such compounds (Biaglow et al. 1984). The aim of this report was to evaluate the effects of cysteamine on heat survival curves at lower temperatures (42.5° C and 41.8° C). At these temperatures, the induction and development of thermotolerance have been shown to occur during the time of heating. We addressed the following questions: (a) to which extent the generation of activated oxygen species by cysteamine might be involved in the interaction between heat and cysteamine treatment at these temperatures; (b) the influence of cell density, and (c) the comparison of cysteamine with the thiol compound aminopropylamino-ethylthiophosphate (WR2721).

This work was supported by grants SFB 324/Is-B3 from the Deutsche Forschungsgemeinschaft. Part of the work was presented at the 11th Annual Meeting of the American Association for Cancer Research (AACR), Los Angeles, CA, 1986.