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Titolo:
Depentylation of the rat esophageal carcinogen, methyl-N-pentylnitrosamine, by microsomes from various human and rat tissues and by cytochrome P450 2A3
Autore:
Chen, SC; Zhou, L; Ding, XX; Mirvish, SS;
Indirizzi:
Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 ppley Inst Res Canc, Omaha, NE 68198 USA Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 Biochem & Mol Biol, Omaha, NE 68198 USA Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 Dept Pharmaceut Sci, Omaha, NE 68198 USA SUNY Albany, Sch Publ Hlth, Albany, NY USA SUNY Albany Albany NY USASUNY Albany, Sch Publ Hlth, Albany, NY USA New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA New York State Dept Hlth Albany NY USA th, Wadsworth Ctr, Albany, NY USA
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 9, volume: 29, anno: 2001,
pagine: 1221 - 1228
SICI:
0090-9556(200109)29:9<1221:DOTREC>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIVER-MICROSOMES; METABOLIC-ACTIVATION; NITROSO-COMPOUNDS; DNA METHYLATION; HUMAN CANCER; EXPRESSION; ENZYMES; NITROSOBENZYLMETHYLAMINE; N'-NITROSONORNICOTINE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Mirvish, SS Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 es Canc, Omaha, NE 68198 USA
Citazione:
S.C. Chen et al., "Depentylation of the rat esophageal carcinogen, methyl-N-pentylnitrosamine, by microsomes from various human and rat tissues and by cytochrome P450 2A3", DRUG META D, 29(9), 2001, pp. 1221-1228

Abstract

Methyl-n-pentylnitrosamine (MPN) is carcinogenic for the rat esophagus. Todetermine organ specificity for MPN activation by human tissues, microsomes isolated from human organs (snap-frozen <6 h after death or removed surgically) were incubated with [pentyl-H-3]MPN, and [H-3]pentaldehyde formationwas measured by high-pressure liquid chromatography of its 2,4-dinitrophenylhydrazone using radioflow assay. With 100 <mu>M MPN, mean depentylation rates were 6.6 (liver), 2.9 to 3.8 (kidney, stomach, small intestine, and colon), and 0.4 to 1.6 (esophagus, lung, and skin) pmol of pentaldehyde/mg ofprotein/min. Of 14 human esophagi, four showed relatively high depentylation rates of 3.3 to 4.1 pmol/mg/min. Apparent K-m was 80 to 160 muM (V-max, 3-15 pmol/mg/min) for three esophagi, 90 to 130 (2 livers), and 1330 (1 kidney) muM. Rat tissues showed mean depentylation rates for 100 muM MPN of 24.9 (liver), 14.5 (esophagus), 7.0 (lung), and 0.0 to 2.7 (5 other tissues) pmol/mg/min. MPN depentylation by rat cytochrome P450 2A3 showed an apparent K-m of 8 muM (V-max, 70 pmol/nmol of P450/min) and was competitively inhibited by the CYP2A inhibitor coumarin (apparent K-i, 4 muM). Coumarin (0.4 mM) inhibited microsomal depentylation of 100 muM MPN by 37 to 62% for human esophagus, liver, kidney, and colon and for rat esophagus but not for ratliver and lung. MPN depentylation by rat esophageal microsomes increased up to 90% on adding P450 reductase. The results indicate organ-specific MPN metabolism by rat but not human esophagus. Nevertheless, the relatively high activity of four human esophagi might indicate increased susceptibility of some individuals to carcinogenesis by unsymmetrical dialkylnitrosamines.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 19:32:29