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 lipoxygenase purified from human term placenta of nonsmoking women and intrauterine 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 generating several soluble and protein-bound metabolites of benzo(a)pyrene-7,8-dihydrodiol. The co-oxidation was inhibited significantly by the specific lipoxygenase inhibitor, nordihydroguaiaretic acid. Substitution for the active enzyme in the reaction mixture with heat denatured enzyme resulted in almost complete abolition of benzo(a)pyrene-7,8-dihydrodiol co-oxidation. These results suggest that lipoxygenase in the placentas and intrauterine conceptal tissues is capable of metabolizing benzo(a)pyrene-7,8-dihydrodiol to several reactive metabolites and may represent one of the major xenobiotic metabolizing pathways of bioactivating chemicals in the intrauterine compartment.