The effect of caffeine on the cytotoxicity of misonidazole and some other nitroheterocyclic compounds

Caffeine was found to potentiate the cytotoxic effect of misonidazole (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) towards mammalian cells in vitro. This enhancement of toxicity is shown to occur under both aerobic and hypoxic conditions. Split dose experiments indicate that the general shape of the hypoxic survival curve can be restored by exposure of cells to O₂ between doses. Exposure of cells to 2 mM caffeine during the split dose experiment has no potentiating effect. Further experiments showed that caffeine affects the expression of misonidazole-induced potentially lethal damage. Other electron-affinic nitro compounds which show greater toxicity to hypoxic compared to aerobic cells, viz. metronidazole and nitrofurantoin, also have their toxicities enhanced by subsequent exposure to caffeine.