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Titolo:
CONSEQUENCES OF 3-METHYLCHOLANTHRENE-TYPE INDUCTION FOR THE METABOLISM OF 4-AMINOBIPHENYL IN ISOLATED RAT HEPATOCYTES
Autore:
ORZECHOWSKI A; SCHRENK D; SCHUT HAJ; BOCK KW;
Indirizzi:
UNIV TUBINGEN,INST TOXICOL,WILHELMSTR 56 D-72074 TUBINGEN GERMANY UNIV TUBINGEN,INST TOXICOL D-72074 TUBINGEN GERMANY MED COLL OHIO,DEPT PATHOL TOLEDO OH 43614
Titolo Testata:
Carcinogenesis
fascicolo: 3, volume: 15, anno: 1994,
pagine: 489 - 494
SICI:
0143-3334(1994)15:3<489:CO3IFT>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARCINOGENIC AROMATIC-AMINES; HEPATIC-MICROSOMAL PREPARATIONS; N-HYDROXY ARYLAMINES; URINARY-BLADDER; DNA ADDUCTS; LIVER; INVIVO; GLUCURONIDATION; OXIDATION; HEMOGLOBIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
A. Orzechowski et al., "CONSEQUENCES OF 3-METHYLCHOLANTHRENE-TYPE INDUCTION FOR THE METABOLISM OF 4-AMINOBIPHENYL IN ISOLATED RAT HEPATOCYTES", Carcinogenesis, 15(3), 1994, pp. 489-494

Abstract

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 N-hydroxylation and alternative metabolic pathways in the hepatocyte. In freshly isolated rat hepatocytes,4-ABP (at a substrate concentration of 10 mu M) was mainly N-acetylated (54% of total metabolites), while 2% N-hydroxy-4-ABP-N-glucuronide and 21% of unconjugated N-hydroxylated metabolites were detectable. Ring-hydroxylated metabolites and the primary N-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 N-acetylated (2% of total metabolites) and an increase of N-hydroxylated(54% as free and glucuronidated compound) and ring-hydroxylated (35%)metabolites. Essentially similar effects were seen at a substrate concentration of 50 mu M. Consistently, MC-type induction with beta-naphthoflavone resulted in a significant increase in the formation of DNA adducts of 4-ABP, detected by P-32-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 toN-oxidation. However, N-hydroxy-4-ABP (in contrast to N-hydroxy-2-NA)is mostly released from hepatocytes in the unconjugated form.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 09:07:23