|
|||||
|
|
Biotransformation of the cyclopenta-fused polycyclic aromatic hydrocarbon benz[j]aceanthrylene in isolated rat liver cells: identification of nine new metabolites |
|
| Authors: | Nyholm, Solfrid H. Alexander, Jan Lundanes, Elsa Frandsen, Henrik Andersson, Rolf Grivas, Spiros Nesnow, Stephen Holme, JOrn A. |
| Affiliation: | 1Department of Environmental Medicine, National Institute of Public Health PO Box 4404 Torshov, N-0462 Oslo, Norway 2Department of Chemistry, University of Oslo PO Box 1033 Blindem, N-0315 Oslo, Norway 3Institute of Toxicology, National Food Agency of Denmark Mørkhøj Bygade 19, DK-2860 SØborg, Denmark 4Department of Chemistry, Swedish University of Agricultural Science PO Box 7016, S-75007 Uppsala, Sweden 5Environmental Carcinogenesis Division, US Environmental Protection Agency NC 27711, USA |
| Abstract: | The biotransformation of benz[j]aceanthrylene (B[j]A) was studiedin suspensions of hepatocytes isolated from Aroclor 1254-treatedor untreated rats. Using radiolabeled cofactors and metabolicinhibitors combined with UV, mass and 1H-NMR spectroscopy, wehave detected five known metabolites and characterized ninenew metabolites: metabolite 1 was tentatively assigned as B[j]A-l,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; metabolite4, B[j]A-l-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 conjugateand two sulfate conjugates of a B[j]A-metabolite; metabolite8, B[j]A-10-O-glucuronide; metabolite 8', B[j]A-1,2-dihydrodiol;meta-bolite 9, B[j]A-10-sulfate; metabolite 9', B[j]A-9,10-dihydrodioland metabolite 10, B[j]A-9,10-dihydro-9-hydroxy-10-sulfate.The metabolites identified support the notion that epoxidationat the cyclopenta region is an important activation step ofB[j]A. Furthermore, sulfation appears to play a very importantrole in the conversion of hydroxylated B[j]A metabolites intomore polar excretable products. |
| Keywords: | |
| 本文献已被 Oxford 等数据库收录！ | |