Peroxidase-catalyzed oxidation of (bi)sulfite: reaction of free radical metabolites of (bi)sulfite with (+/-)-7,8-dihydroxy-7, 8-dihydroxy[a]pyrene.

Abstract

The peroxidase-catalyzed metabolism of (bi)sulfite (hydrated sulfur dioxide) in the presence of (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was examined. Both horseradish peroxidase and prostaglandin peroxidase catalyze the one-electron oxidation of (bi)sulfite. This results in the formation of a sulfur trioxide radical anion which then reacts with molecular oxygen to form a peroxyl radical. This (bi)sulfite-derived peroxyl radical then reacts with BP-7,8-diol to form BP-7,8-diol-9,10-epoxides, the ultimate carcinogenic form of benzo[a]pyrene (BP). Addition of (bi)sulfite to incubations containing BP-7,8-diol and an active peroxidase resulted in significantly increased levels of BP diol-epoxide formation. This result may, in part, explain the reported co-carcinogenic effect of sulfur dioxide on BP-induced tumors in the respiratory tracts of rats and hamsters. The sulfur trioxide radical anion also reacts directly with BP-7,8-diol to form a sulfonate adduct. This reaction was particularly significant under conditions where molecular oxygen was depleted from the incubations. While the significance of this particular adduct is not known, its formation suggests that the sulfur trioxide radical anion generated during the peroxidase-catalyzed oxidation of (bi)sulfite could react with a wide assortment of compounds to form sulfonate adducts.