Biotransformation of the cyclopenta-fused polycyclic aromatic hydrocarbon benz[j]aceanthrylene in isolated rat liver cell: identification of nine new metabolites.
The biotransformation of benz[j]aceanthrylene (B[j]A) was studied in suspensions of hepatocytes isolated from Aroclor 1254-treated or untreated rats. Using radiolabeled cofactors and metabolic inhibitors combined with UV, mass and 1H-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 of 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-metabolite; 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-sulfate. The metabolites identified support the notion that epoxidation at the cyclopenta region is an important activation step of B[j]A. Furthermore, sulfation appears to play a very important role in the conversion of hydroxylated B[j]A metabolites into more polar excretable products.
Nyholm
S H
SH
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Alexander
J
J
Lundanes
E
E
Frandsen
H
H
Andersson
R
R
Grivas
S
S
Nesnow
S
S
Holme
J A
JA
D000818:Animals; D001711:Biotransformation; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008748:Methylcholanthrene / Q000031:analogs & derivatives* / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009153:Mutagens; D008748:Methylcholanthrene; C037411:benz(j)aceanthrylene