The effects of reduction products of misonidazole on Chinese hamster ovary cells.
Electrolytic reduction of the hypoxic cell sensitizer, misonidazole, was performed under hypoxic conditions at a controlled potential of -800 mV relative to a standard calomel electrode, High performance liquid chromatography (HPLC) separation of the reduction product(s) of [14C] misonidazole yielded two radioactive peaks, a major one containing 70 to 80% of the total activity and a minor one, containing 20 to 30%. A six hour hypoxic exposure of Chinese hamster ovary cells at 37 degrees C to a 1 mM equivalent of unseparated reduction product(s) resulted in less toxicity than a similar exposure to misonidazole alone. The corresponding cellular uptake and binding of reduced misonidazole was the same under aerobic or hypoxic conditions, but up to an order of magnitude lower compared to a hypoxic misonidazole exposure.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D008920:Misonidazole / Q000378:metabolism / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D010053:Ovary; D010084:Oxidation-Reduction
D009593:Nitroimidazoles; D008920:Misonidazole