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Titolo:
Genetic polymorphism of CYP2A6 in relation to cancer
Autore:
Kamataki, T; Nunoya, K; Sakai, Y; Kushida, H; Fujita, K;
Indirizzi:
Hokkaido Univ, Fac Pharmaceut Sci, Lab Drug Metab, Kita Ku, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ Sapporo Hokkaido Japan 0600812 oro, Hokkaido 0600812, Japan
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 428, anno: 1999,
pagine: 125 - 130
SICI:
1386-1964(19990716)428:1-2<125:GPOCIR>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
COUMARIN 7-HYDROXYLATION;
Keywords:
human CYP2A6; Salmonella typhimurium YG7108; N-nitrosamine; lung cancer; polymorphism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
8
Recensione:
Indirizzi per estratti:
Indirizzo: Kamataki, T Hokkaido Univ, Fac Pharmaceut Sci, Lab Drug Metab, Kita Ku, N12W6, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ N12W6 Sapporo Hokkaido Japan 0600812 0812, Japan
Citazione:
T. Kamataki et al., "Genetic polymorphism of CYP2A6 in relation to cancer", MUT RES-F M, 428(1-2), 1999, pp. 125-130

Abstract

To clarify the roles of human cytochrome P450 (P450 or CYP) 2A6 and 2E1 onthe metabolic activation of N-nitrosamines, we established genetically engineered Salmonella typhimurium strains harboring human CYP2A6 or CYP2E1 together with NADPH-P450 reductase (OR). The 5'-terminus of CYP cDNA was modified to achieve a high-level expression in S. typhimurium. Modified CYP2A6 or CYP2E1 cDNA and native OR cDNA were introduced into a pCW vector. S. typhimurium YG7108 cells were transformed with this vector. The mutagen producing ability of these enzymes for some N-nitrosamines were evaluated using the established S. typhimurium cells. We found that the substrate specificityof CYP2A6 and CYP2E1 was different among mutagens. CYP2A6 was responsible for the metabolic activation of N-nitrosamines possessing relatively long alkyl chains, whereas CYP2E1 was responsible for the metabolic activation ofN-nitrosamines with relatively short alkyl chains. It is likely that CYP2A6 gene polymorphism is responsible for the interindividual variability on the cancer susceptibility. We found the whole deletion of CYP2A6 gene as a type of genetic polymorphism in Japanese. Thus, we developed a gene diagnosis method to detect the variant. We evaluated the relationship between the CYP2A6 gene whole deletion and the susceptibility to the lung cancer. The frequency of CYP2A6 gene whole deletion was significantly lower in the lung cancer patients than that of healthy volunteers. (C) 1999 Elsevier Science B. V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 19:15:38