Benzo[a]pyrenedione/benzo[a]pyrenediol oxidation-reduction couples and the generation of reactive reduced molecular oxygen

Abstract

The ability of the isomeric quinone metabolites of benzo[a]pyrene, benzo[a]pyrene-6,12-dione, benzo[a]pyrene-1,6-dione, and benzo[a]pyrene-3,6-dione to undergo reversible, univalent oxidation-reduction cycles involving the corresponding benzo[a]pyrenediols and intermediate semiquinone radicals has been characterized. Under anaerobic conditions, all three benzo[a]pyrenediones are easily reduced to benzo[a]pyrenediols, even by mild biological agents such as NAD(P)H, cysteamine, and glutathione. The benzo[a]pyrenediols, in turn, are very rapidly autoxidized to the benzo[a]pyrenediones when exposed to air. Substantial amounts of hydrogen peroxide are produced during these autoxidations, and other reactive reduced oxygen species, such as the superoxide and hydroxyl radicals, are probably formed transiently as well. The benzo[a]pyrenediol-benzo[a]pyrenedione interconversions proceed by one-electron steps; the corresponsing semiquinone radicals can be monitored by electron spin resonance spectroscopy as inter mediates during these reactions carried out at high pH. Benzo[a]pyrenediones induce DNA strand scission when incubated with bacteriophage T7 DNA. This damage is modified by conditions which indicate that reduced oxygen species propagate the free-radical reactions responsible for the strand scission. Benzo[a]pyrenediones are electron-acceptor substrates for NADH dehydrogenase from Clostridium kluyveri. Catalytic amounds of these benzo[a]pyrene metabolites, together with this respiratory enzyme function as cyclic oxidation-reduction couples which link NADH and molecular oxygen in the continuous production of hydrogen peroxide. These data, together with preliminary results with cells in culture, indicate that benzo[a]pyrenediones are potentially harmful metabolites of benzo[a]pyrene, acting by processes which lead to their regeneration rather than depletion; nucleic acid and call damage is probably produced by the reactive reduced oxygen species resulting from such regenerative oxidation-reduction cycles.

Evidence for the involvement of superoxide in vitamin K-dependent carboxylation of glutamic acid residues of prothrombin

“…The oxidation of quinols and semiquinones to yield superoxides has been described (Cadenas et al, 1977;Lorentzen & Ts'o, 1977;Patel & Willson, 1973), but the involvement of vitamin K in the production of superoxide for the carboxylation reaction has not been considered. As in many reactions in which superoxide is involved, it is difficult to identify the reacting species, because of the possible intervention of reactions such as:…”

Influence of Charcoal Broiled Meat Consumption on the Liver Functions and Non-Enzymatic Antioxidants in Human Blood

“…For example, PAH toxification via the free-radical pathway has received much attention with long time ago. In this regard, studies from the laboratory of Ts'o are interesting; they propose that quinones of PAH owe their activity to oxidation-reduction cycles involving quinone, hydroquinone, and molecular oxygen [30]. The reactive reduced oxygen radicals and semiquinone radicals formed during these cycles have been shown to be mutagenic in bacterial as well as mammalian cells [31,32].…”

Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: Advances and open questions

“…For example, 3-MC treatment of rats enhanced chrysene-3,6-DG formation about 310-fold in liver microsomes, suggesting -in addition to induction of UGT isoforms-an influence of topological features of UGT quaternary structure, discussed subsequently. Glucuronidation of quinols is toxicologically relevant since it probably prevents quinone-quinol redox cycles and associated oxidative stress [33][34][35][36][37]. BaP quinol diglucuronides represent major conjugates in bile and urine after administration of BaP [38,39].…”