Radiosensitisation of cells in vitro with misonidazole: dependence on endogenous sulphydryl.

The radiosensitisation conferred upon hypoxic mammalian cells by misonidazole can be reduced by the addition of exogenous sulphydryl compounds and enhanced by the diminution of endogenous non-protein sulphydryl compounds (NPSH). A similar enhancement of the effect of misonidazole has been demonstrated in bacteria which are genetically low in NPSH. In the experiments reported here, the radiosensitising ability of various concentrations of misonidazole on anoxic populations of a single strain of mammalian cells, containing different amounts of NPSH, has been measured. At misonidazole concentrations of 3mM and less, about twice as much misonidazole was required to confer the same degree of radiosensitisation on the cells which contained a high concentration of NPSH as was needed for cells which contained half the amount of NPSH. At these concentrations, misonidazole did not deplete endogenous NPSH. 5mM misonidazole conferred the same enhancement of sensitivity in both high- and low-NPSH-containing cells. The oxygen enhancement ratio, and extrapolation number of the survival curves, for cells irradiated without misonidazole were not affected by the variation in NPSH.