Biotransformation and DNA Adduct Formation ofTrans-8,9-Dihydroxy-8,9-Dihydrodibenzo[a, l]Pyrene by Induced Rat Liver and Human CYP1A1 Microsomes
| Autor: | Stephen Nesnow, Leon C. King, C. Davis, Guy R. Lambert, Michael H. George, William T. Padgett, Linda D. Adams |
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| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Polycyclic Aromatic Compounds. 16:181-190 |
| ISSN: | 1563-5333 1040-6638 |
| DOI: | 10.1080/10406639908020585 |
| Popis: | In order to explain the adduct patterns observed from the human CYP1A1-mediated binding of dibenzo[a, l]pyrene (DB[a, l]P) to DNA, we have investigated the further metabolism and DNA adduct activity of trans-DB[a, l]P-8,9-diol by induced rat liver and human CYP1A1 microsomes. trans-DB[a, l]P-8,9-diol was synthesized and metabolic studies with β-naphthoflavone-induced rat liver microsomes indicated three major metabolites: 2 diastereomers of trans,trans-8,9,11,12-tetrahydro-8,9,11,12-tetrahydroxy-DB[a, l]P and 8,9,13,14-tetrahydro-8,9,13,14-tetrahydroxy-DB[a, l]P. DB[a, l]P when activated by CYP1A1/epoxide hydrase (EH) and calf thymus DNA gave a complex pattern of DNA adducts most of which cochromatograph with syn- and anti-DB[a, l]P fjord region diol epoxide-DNA standards. Two highly polar eluting adducts were also observed, one which cochromatographs with the single major DNA adduct obtained from the CYP1A1/EH activation of trans-DB[a, l]P-8,9-diol. The relative retention time of this adduct sug... |
| Databáze: | OpenAIRE |
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