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Titolo:
Human cytochrome p450 CYP2A13: Predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
Autore:
Su, T; Bao, ZP; Zhang, QY; Smith, TJ; Hong, JY; Ding, XX;
Indirizzi:
New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA New York State Dept Hlth Albany NY USA 12201 th Ctr, Albany, NY 12201 USA SUNY Albany, Sch Publ Hlth, Albany, NY USA SUNY Albany Albany NY USASUNY Albany, Sch Publ Hlth, Albany, NY USA Univ Med & Dent New Jersey, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey Piscataway NJ USA 08854 scataway, NJ 08854 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 18, volume: 60, anno: 2000,
pagine: 5074 - 5079
SICI:
0008-5472(20000915)60:18<5074:HCPCPE>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LIVER-MICROSOMES; TERT-BUTYL ETHER; NICOTINE C-OXIDATION; HUMAN NASAL-MUCOSA; LUNG-CANCER; COUMARIN 7-HYDROXYLATION; CHEMICAL CARCINOGENESIS; N-NITROSODIALKYLAMINES; ALPHA-HYDROXYLATION; GASOLINE ETHERS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Hong, JY New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA NewYork State Dept Hlth Albany NY USA 12201 lbany, NY 12201 USA
Citazione:
T. Su et al., "Human cytochrome p450 CYP2A13: Predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone", CANCER RES, 60(18), 2000, pp. 5074-5079

Abstract

The human CYP2A subfamily comprises three genes, CYP2A6, CYP2A7, and CYP2A13. CYP2A6 is active toward many carcinogens and is the major coumarin 7-hydroxylase and nicotine C-oxidase in the liver, whereas CYP2A7 is not functional. The function of CYP2A13 has not been characterized. In this study, a CYP2A13 cDNA was prepared by RNA-PCR from human nasal mucosa and was translated using a baculovirus expression system. In a reconstituted system, the expressed CYP2A13 was more active than CYP2A6 in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, andN-nitrosomethylphenylamine but was much less active than CYP2A6 in coumarin 7-hydroxylation. Of particular interest, CYP2A13 was highly active in themetabolic activation of a major tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, with a catalytic efficiency much greaterthan that of other human cytochrome P450 isoforms examined previously. Thetissue distribution of CYP2A13 was determined with isoform-specific RNA-PCR. CYP2A13 mRNA was detected in liver and a number of extrahepatic tissues,including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle. Quantitative PCR analysisfurther revealed that CYP2A13 mRNA is expressed at the highest level in the nasal mucosa, followed by the lung and the trachea. Together, these findings suggest that CYP2A13 plays important roles in xenobiotic toxicity and tobacco-related tumorigenesis in the human respiratory tract.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 23:04:05