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 mu M Cu2+ or 15 mu M ferricytochrome c (cyt c(3+)) 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 17 beta-hydroxysteroid dehydrogenase (17 beta-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 17 beta-HSD, cyt c(3+) does not inhibit the enzyme. If cyt c(3+) 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 PAW o-quinone cycling if certain metal ions or metal chelates are also present. (C) 1998 Elsevier Science Ltd. All rights reserved.