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Titolo:
CYTOSOLIC ACTIVATION OF AROMATIC AND HETEROCYCLIC AMINES - INHIBITIONBY DICOUMAROL AND ENHANCEMENT IN VIRAL-HEPATITIS-B
Autore:
DEFLORA S; BENNICELLI C; DAGOSTINI F; IZZOTTI A; CAMOIRANO A;
Indirizzi:
UNIV GENOA,INST HYG & PREVENT MED,VIA A PASTORE 1 I-16132 GENOA ITALY
Titolo Testata:
Environmental health perspectives
, volume: 102, anno: 1994, supplemento:, 6
pagine: 69 - 74
SICI:
0091-6765(1994)102:<69:CAOAAH>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROSTAGLANDIN ENDOPEROXIDE SYNTHETASE; METABOLIC-ACTIVATION; GLUTAMIC-ACID; DT-DIAPHORASE; MUTAGENICITY; LIVER; HEPATOCARCINOGENS; FRACTIONS; BINDING; DNA;
Keywords:
AROMATIC AMINES; HETEROCYCLIC AMINES; METABOLISM; CYTOSOL; MUTAGENICITY; DICOUMAROL; DT DIAPHORASE; VIRAL HEPATITIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
S. Deflora et al., "CYTOSOLIC ACTIVATION OF AROMATIC AND HETEROCYCLIC AMINES - INHIBITIONBY DICOUMAROL AND ENHANCEMENT IN VIRAL-HEPATITIS-B", Environmental health perspectives, 102, 1994, pp. 69-74

Abstract

The aromatic amines 2-aminofluorene (2AFI, 2-acetylaminofluorene, and2-aminoanthracene, and the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinol and 3-amino-1-methyl-SH-pyrido[4,3-b]indole (Trp-P-2) were activated by ratliver cytosolic fractions to form mutagenic metabolites in Salmonellatyphimurium strains TA98, TA98NR, and TA98/1,8-DNP6. In the case of the Trp-P-2, the cytosolic activation was even more potent than the microsomal activation, which is classically ascribed to N-hydroxylation and subsequent esterification. The cytosolic activation was a) NADPH-dependent, b) induced by pretreatment of rats with 3-methylcholanthrene and especially Aroclor 1254 but not by phenobarbital, and c) inhibitedby dicoumarol. The hypothesis is that, following a preliminary oxidative step in the cytosol (pure cytosolic activation) or in microsomes via prostaglandin H synthase (mixed microsomal-cytosolic activation), an oxidized intermediate of amino compounds may serve as substrate for DT diaphorase activity and bielectronically reduced to the corresponding N-hydroxyamino derivative. Purified DT diaphorase, in the presence of either NADPH or NADH as electron donor, produced mutagenic derivatives from IQ and Trp-P-2. An NADPH-dependent activation of Trp-P-2! also occurred in the liver cytosol of woodchucks (Marmota monax), but wasnot inhibited by dicoumarol. As previously demonstrated with liver S-12 fractions in both humans and woodchucks, the cytosolic activation of Trp-P-2 was enhanced in animals affected by hepatitis B virus infection. This enhanced metabolism, which persisted even after appearance of primary hepatocellular carcinoma in virus carriers, is likely to be ascribed to mechanisms other than DT diaphorase induction, such as glutathione depletion.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 03:31:00