THE OXIDATION OF ASCORBATE BY ELECTRON AFFINIC DRUGS AND CARCINOGENS

Abstract— The nitrobenzenes, the carcinogens 4-nitropyridine- N -oxide and 4-nitro-quinoline- N -oxide as well as the nitrofurans, also known to be carcinogenic, have been found to enhance the reaction of ascorbate with oxygen. The reaction results in the oxidation of ascorbate, the production of dehydroascorbate, superoxide radical, peroxide and water. The drugs are not reduced to stable intermediates during the oxidation but are recycled to their original state. The oxygen consumption is partially inhibited by either superoxide dismutase or catalase. If both superoxide dismutase and catalase are included in the reaction mixture, total oxygen consumption was equal to the amount expected for oxidation of ascorbate to dehydroascorbate and reduction of oxygen to water. The oxygen consumption was inhibited by ferricytochrome c. Semiquinones, nitro and hydroxylamine radicals, produced by electron transfer from ascorbate, reduce ferricytochrome c. These oxygen reactive radicals are responsible for the stimulation of oxygen utilization and ascorbate oxidation. In addition we have found that Ehrlich cells, containing catalase and superoxide dismutase, inhibit the drug catalyzed oxidation of ascorbate. The presence of cyanide, known to inhibit catalase and superoxide dismutase, abolished the cell effect for most of the drugs tested.