Prostaglandin H synthase oxidation of benzidine and o-dianisidine: reduction and conjugation of activated amines by thiols

Abstract
Prostaglandin H synthase oxidized the carcinogens benzidine and o-dianisidine to their respective quinonediimines. Analysis of the reaction media by u.v./visible spectroscopy and liquid chromatography with electrochemical and radiochemical detection revealed that these quinonediimines can be both conjugated and reduced by glutathione, cysteine and N-acetyl-cysteine. Analysis of the purified conjugate formed between synthetic benzidinediimine and glutathione by proton magnetic resonance spectroscopy demonstrated the product to be 3-(glutathion-S-yl)-benzidine. This metabolite was also formed during peroxidation of benzidine by prostaglandin H synthase in the presence of excess glutathione. These conjugates may be useful markers of peroxidatic activation of aromatic amines in vivo.

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