| Autor: |
Orzechowski, Achim, Schrenk, Dieter, Schut, Herman A.J., Bock, Karl W. |
| Zdroj: |
Carcinogenesis; 1994, Vol. 15 Issue 3, p489-494, 6p |
| Abstrakt: |
Carcinogenic aromatic amines such as 4-aminobiphenyl (4-ABP) are extensively metabolized by both oxidative and conjugation reactions. Thus the burden of genotoxic metabolites of 4-ABP in a target organ is probably influenced by the balance of -hydroxylation and alternative metabolic pathways in the hepatocyte. In freshly isolated rat hepatocytes, 4-ABP (at a substrate concentration of 10 μM) was mainly -acetylated (54% of total metabolites), while 2% Ar-hydroxy-4-ABP--glucuronide and 21% of unconjugated -hydroxylated metabolites were detectable. Ring-hydroxylated metabolites and the primary -glucuronide of 4-ABP accounted for 8% and 4%, respectively. Pretreatment of rats with 3-methylcholanthrene (MC), a dioxin-type inducer of CYP1A isozymes and phenol UDP-glucuronosyltransferase (UGT1A1), led to a dramatic decrease of W-acetylated (2% of total metabolites) and an increase of -hydroxylated (54% as free and glucuronidated compound) and ring-hydroxylated (35%) metabolites. Essentially similar effects were seen at a substrate concentration of 50 μM. Consistently, MC-type induction with β-naphthoflavone resulted in a significant increase in the formation of DNA adducts of 4-ABP, detected by P-postlabelling of hepatocellular DNA. The results suggest that, similar to a previous study with 2-naphthylamine (2-NA), MC treatment leads to a marked shift from conjugation to -oxidation. However, -hydroxy-4-ABP (in contrast to -hydroxy-2-NA) is mostly released from hepatocytes in the unconjugated form. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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