Energy and misonidazole toxicity: the effects of 5-thio-D-glucose.

ABSTRACT

Cell inactivation and DNA damage (single-strand breaks) were used to study the effects of inhibitors of anaerobic glucose oxidation on the toxicity of misonidazole to hypoxic Chinese hamster cells. Citrate and 2-deoxyglucose produced no effects on the toxicity. 5-thio-D-glucose (5-TG) protected cells of the CH2B2 line to some extent (SSB decreased by about 30%). In the CHO lines used (wild, and ethylmethanesulfonate-sensitive mutants), 5-TG had varied effects. Non-protein sulfhydryl (NPSH) levels were measured in all lines. Cells with lower NPSH levels are more sensitive to misonidazole; these are the cells which are protected by 5-TG. Cell line variations must be considered when studying interactions between a drug and other forms of treatment as possible treatments of cancer.