Redox cycling of polycyclic aromatic hydrocarbon o-quinones: metal ion-catalyzed oxidation of catechols bypasses inhibition by superoxide dismutase.

Several two-electron quinone reductases catalyze the redox cycling of polycyclic aromatic hydrocarbon (PAH) o-quinones. When the carbonyl reductase of human placenta catalyzes the cycling of 9,10-phenanthrenequinone in aqueous phosphate buffer, reactive oxygen species are produced. Superoxide dismutase (SOD) inhibits the cycling by more than 90%, but the addition of 1 microM Cu2+ or 15 microM ferricytochrome c (cyt c3+) completely restores the cycling rate to that of the control. Similar results are obtained for 5,6-chrysenequinone, 5,6-benz[a]anthracenequinone, 4,5-benzo[a]pyrenequinone, and 7,8-benzo[a]pyrenequinone in assay mixtures which contain dimethyl sulfoxide. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) of human placenta also catalyzes the redox cycling of these quinones, and cycling is inhibited by SOD. Although free metal ions (Cu2+ and Fe3+) inhibit the 17beta-HSD, cyt c3+ does not inhibit the enzyme. If cyt c3+ is added to assay mixtures containing SOD, cycling rates are equal to those of the corresponding controls. These experiments suggest that SOD may not protect cells from the toxic effects of PAH o-quinone cycling if certain metal ions or metal chelates are also present.