BIOACTIVATION OF BENZO(A)PYRENE-7,8-DIHYDRODIOL CATALYZED BY LIPOXYGENASE PURIFIED FROM HUMAN TERM PLACENTA AND CONCEPTAL TISSUES

Bioactivation of C-14-benzo(a)pyrene-7,8-dihydrodiol catalyzed by lipo xygenase purified from human term placenta of nonsmoking women and int rauterine conceptal tissues (at 4 weeks of gestation) was investigated . Incubation of C-14-benzo(a)pyrene-7,8-dihydrodiol with 3 mM linoleic acid in the presence of lipoxygenase purified from either human term placenta or intrauterine conceptal tissues resulted in co-oxidation ge nerating several soluble and protein-bound metabolites of benzo(a)pyre ne-7,8-dihydrodiol. The co-oxidation was inhibited significantly by th e specific lipoxygenase inhibitor, nordihydroguaiaretic acid. Substitu tion for the active enzyme in the reaction mixture with heat denatured enzyme resulted in almost complete abolition of benzo(a)pyrene-7,8-di hydrodiol co-oxidation. These results suggest that lipoxygenase in the placentas and intrauterine conceptal tissues is capable of metabolizi ng benzo(a)pyrene-7,8-dihydrodiol to several reactive metabolites and may represent one of the major xenobiotic metabolizing pathways of bio activating chemicals in the intrauterine compartment.