LINOLEATE-DEPENDENT COOXYGENATION OF BENZO(A)PYRENE AND BENZO(A)PYRENE-7,8-DIHYDRODIOL BY RAT CYTOSOLIC LIPOXYGENASE

被引:10
作者
BYCZKOWSKI, JZ
KULKARNI, AP
机构
[1] Toxicology Program, College of Public Health, University of South Florida, MHH-104, Tampa, FL
关键词
D O I
10.3109/00498259209053124
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Co-oxygenation of C-14-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-mu-M of the lipoxygenase inhibitor and antioxidant NDGA. 5. It is postulated that the lineoleic 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.
引用
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页码:609 / 618
页数:10
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