Linoleate-dependent co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by rat cytosolic lipoxygenase.
1. Co-oxygenation of 14C-labelled benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol was studied in rat lung cytosol, using linoleic acid as a co-substrate. Covalently bound and soluble metabolites were quantified by radiometry and h.p.l.c., respectively. 2. The co-oxygenation resulted in the production of reactive metabolites capable of protein binding as well as a series of soluble derivatives. 3. Co-oxygenation of benzo(a)pyrene yielded primarily a significant amount of benzo(a)pyrene-6,12-dione while benzo(a)pyrene-7,8-dihydrodiol led to a significant amount of benzo(a)pyrene-trans-anti-tetrol. 4. Their production was abolished by addition of 25 microM of the lipoxygenase inhibitor and antioxidant NDGA. 5. It is postulated that the linoleic acid peroxyl radicals, formed by rat lung lipoxygenase, initiate the one-electron oxidation of benzo(a)pyrene to its quinones, and epoxidation of benzo(a)pyrene-7,8-diol to the ultimate carcinogenic benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide.
Byczkowski
J Z
JZ
Toxicology Program, College of Public Health, University of South Florida, Tampa 33612.
Kulkarni
A P
AP
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008084:Lipoxygenase / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000201:enzymology; D009637:Masoprocol / Q000494:pharmacology; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004101:Dihydroxydihydrobenzopyrenes; D005609:Free Radicals; D008041:Linoleic Acids; D010545:Peroxides; D011506:Proteins; C017228:benzo(a)pyrene 7,8-dihydrodiol; C049375:perhydroxyl radical; D001564:Benzo(a)pyrene; D009637:Masoprocol; D019787:Linoleic Acid; D008084:Lipoxygenase