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Titolo:
CYTOCHROME-P450 2A OF NASAL EPITHELIUM - REGULATION AND ROLE IN CARCINOGEN METABOLISM
Autore:
BEREZIAT JC; RAFFALLI F; SCHMEZER P; FREI E; GENESTE O; LANG MA;
Indirizzi:
INT AGCY RES CANC,MECHANISMS CARCINOGENESIS UNIT,150 COURS ALBERT THOMAS F-69372 LYON 08 FRANCE INT AGCY RES CANC,MECHANISMS CARCINOGENESIS UNIT F-69372 LYON 08 FRANCE DEUTSCH KREBSFORSCHUNGSZENTRUM,DIV TOXICOL & ENVIRONM CARCINOGENESIS W-6900 HEIDELBERG GERMANY
Titolo Testata:
Molecular carcinogenesis
fascicolo: 2, volume: 14, anno: 1995,
pagine: 130 - 139
SICI:
0899-1987(1995)14:2<130:C2ONE->2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
OLFACTORY-SPECIFIC CYTOCHROME-P-450; HUMAN-LIVER-MICROSOMES; RABBIT NASAL; RAT LUNG; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE NNK; NADPH-CYTOCHROME-P-450 REDUCTASE; BIOTRANSFORMATION ENZYMES; COUMARIN 7-HYDROXYLATION; N-NITROSODIALKYLAMINES; MONO-OXYGENASES;
Keywords:
NITROSAMINES; AFLATOXIN B-1; METABOLISM; CYP2A-5; REGULATION; NASAL EPITHELIUM; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
J.C. Bereziat et al., "CYTOCHROME-P450 2A OF NASAL EPITHELIUM - REGULATION AND ROLE IN CARCINOGEN METABOLISM", Molecular carcinogenesis, 14(2), 1995, pp. 130-139

Abstract

In this study, we found that rat nasal coumarin-7-hydroxylase (COH) activity was two orders of magnitude higher than rat hepatic COH activity and could be induced by adding coumarin to the rats' drinking water. In western blot analysis, an anti-cytochrome P450 (Cyp) 2a-5 (mouse liver COH) antibody recognized a sharp band in the microsomal fractionof rat nasal epithelium but not of the liver; the band comigrated with Cyp2a-5. The intensity of the band was increased by the coumarin treatment. Similarly, in northern blot analysis, a cDNA probe specific for Cyp2a-5 recognized an mRNA in the nasal epithelium having the same size as mouse liver Cyp2a-5 mRNA; however, no hybridizable mRNA was recognized in liver preparations. Unlike the protein level, the level of the mRNA was not increased by coumarin. When northern blot analyses were performed with two oligoprobes specific for rat lung CYP2A3, an mRNA of similar size to Cyp2a-5 mRNA was recognized. In immunoinhibition analysis, anti-Cyp2a-5 antibody inhibited rat nasal COH activity and aflatoxin B-1 (AFB(1)) metabolism completely. It inhibited N-nitrosodiethylamine (NDEA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by 80-90%. In contrast, the hepatic metabolism of the four compounds was not affected by the antibody. When coumarin instead of anti-Cyp2a-5 antibody was used, a strong but variable inhibition ofthe nasal metabolism of AFB(1), NDEA, and NNK was seen. The results suggest that an enzyme or enzymes similar to mouse liver Cyp2a-5, one of which may be CYP2A3, is expressed at high levels in rat nasal epithelium but not in the liver and that its expression is increased by coumarin, an odorant and a substrate of Cyp2a-5. The increase probably occurs by protein stabilization or stimulation of translation. The results also show that the enzyme has a key role in the nasal metabolism of three well-known carcinogens, AFB(1), NDEA, and NNK and may therefore be an important contributing factor in nasal carcinogenesis. (C) 1995 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 18:02:50