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Titolo:
Determination of coumarin metabolism in Turkish population
Autore:
Cok, I; Kocabas, NA; Cholerton, S; Karakaya, AE; Sardas, S;
Indirizzi:
Gazi Univ, Fac Pharm, Dept Toxicol, TR-06330 Ankara, Turkey Gazi Univ Ankara Turkey TR-06330 , Dept Toxicol, TR-06330 Ankara, Turkey Univ Newcastle Upon Tyne, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England Univ Newcastle Upon Tyne Newcastle Upon Tyne Tyne & Wear England NE2 4HH
Titolo Testata:
HUMAN & EXPERIMENTAL TOXICOLOGY
fascicolo: 4, volume: 20, anno: 2001,
pagine: 179 - 184
SICI:
0960-3271(200104)20:4<179:DOCMIT>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LIVER-MICROSOMES; NICOTINE C-OXIDATION; INTERINDIVIDUAL VARIABILITY; CYTOCHROME-P450 CYP2A6; 7-HYDROXYLASE ACTIVITY; GENETIC-POLYMORPHISM; DELETION; IDENTIFICATION; CANCER; 7-HYDROXYCOUMARIN;
Keywords:
coumarin; coumarin 7-hydroxylation; CYP2A6; interindividual variability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Sardas, S Gazi Univ, Fac Pharm, Dept Toxicol, TR-06330 Ankara, Turkey GaziUniv Ankara Turkey TR-06330 icol, TR-06330 Ankara, Turkey
Citazione:
I. Cok et al., "Determination of coumarin metabolism in Turkish population", HUM EXP TOX, 20(4), 2001, pp. 179-184

Abstract

Cytochrome P450 2A6 is an important human hepatic P450 which activates precarcinogens and oxidizes some drug constituents such as coumarin, halothane, and the major nicotine C-oxidase. Genetic polymorphism exists in the CYP2A6gene. CYP2A6*1 (wildtype) is responsible for the 7-hydroxylation of coumarin. The point mutation (T to A) in codon 160 leads to a single amino acid substitution (Leu to His) and the resulting protein, CYP2A*2 is unable to 7-hydroxylate coumarin. Gene conversion in exons 3, 6, and 8 between the CYP2A6 and the CTP2A7 genes creates another variant, CYP2A6*3. In this study, healthy male and female Turkish volunteers (n = 50) were administered 2 mg coumarin, and urine samples were analyzed for their content of the coumarinmetabolite, 7-hydroxycoumarin (70HC), by high- performance liquid chromatography(HPLC). Genetic polymorphism for CYP2A6 was detected by using two-step polymerase chain reaction (PCR) to identify CYP2A6*1, CYP2A6"2, and CYP2A6*3 in 13 of these subjects. The percentage of the dose excreted of total 70HC in relation to CYP2A6 genotype and excretion of nicotine/cotinine was also evaluated to demonstrate the role of CYP2A6 in nicotine metabolism. Themajority of Turkish subjects (68%) excreted less than 60% of the 2-mg doseas coumarin metabolite. The allelic frequencies were detected as 0.88 for CYP2A6*1 allele; 0.12 for CYP2A6*3 allele in 13 individuals. No heterozygous and homozygous individuals were identified for the CYP2A6"2 allelic variant. Phenotyping and genotyping for drug metabolizing enzymes are of great importance in studies correlating precarcinogen activation or drug metabolism to the CYP2A6 genotype in smoking behavior when populations are investigated.

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Documento generato il 30/05/20 alle ore 14:55:03