BIOTRANSFORMATION OF THE CYCLOPENTA-FUSED POLYCYCLIC AROMATIC HYDROCARBON BENZ[J]ACEANTHRYLENE IN ISOLATED RAT-LIVER CELLS - IDENTIFICATIONOF 9 NEW METABOLITES

The biotransformation of benz[j]aceanthrylene (B[j]A) was studied in s uspensions of hepatocytes isolated from Aroclor 1254-treated or untrea ted rats, Using radiolabeled cofactors and metabolic inhibitors combin ed with UV, mass and H-1-NMR spectroscopy, we have detected five known metabolites and characterized nine new metabolites: metabolite 1 was tentatively assigned as B[j]A-1,2-dihydrodiol-8-sulfate; metabolite 2, B[j]A-1,2,9,10-tetrahydrotetrol; metabolite 3, B[j]A-1,2-dihydrodiol- 10-O-glucuronide; metabolite 4, B[j]A-1-one-8-sulfate; metabolite 5, B [j]A-1,2-dihydrodiol-10-sulfate; metabolite 6, the sulfate conjugate o f B[j]A-dihydrodiol-phenol; peak 7 in the chromatogram is a mixture of one glutathione conjugate and two sulfate conjugates of a B[j]A-metab olite; metabolite 8, B[j]A-10-O-glucuronide; metabolite 8', B[j]A-1,2- dihydrodiol; metabolite 9, B[j]A-10-sulfate; metabolite 9', B[j]A-9,10 -dihydrodiol and metabolite 10, B[j]A-9,10-dihydro-9-hydroxy-10-sulfat e. The metabolites identified support the notion that epoxidation at t he cyclopenta region is an important activation step of B[j]A. Further more, sulfation appears to play a very important role in the conversio n of hydroxylated B[j]A metabolites into more polar excretable product s.