Competitive Dose-modification between Ascorbate and Misonidazole in Human and Hamster Cells: Effects of Glutathione Depletion

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Abstract
Depletion of glutathione by pretreatment with buthionine sulphoximine greatly enhances the radiosensitizing efficiency of misonidazole in mammalian cells in vitro, but a similar effect has not yet been observed in vivo. In thiol-depleted V79 Chinese hamster cells and human HT1080 fibrosarcoma cells, physiological concentrations of ascorbate greatly reduce misonidazole radiosensitization, although there is little effect of ascorbate on misonidazole sensitization in untreated cells. The effect of ascorbate on misonidazole radiosensitization is not markedly dependent on the extracellular concentration of ascorbate; this may be explained by the non-equilibrium uptake of ascorbate at different extracellular concentrations. Failure to obtain a large enhancement of misonidazole radiosensitization as a result of buthionine sulphoximine treatment in vivo may be due, in part at least, to the presence of ascorbate.

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