CYP1A2 and NAT2 genotype/phenotype relations and urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in a human dietary intervention study

2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display...

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Veröffentlicht in:Food and chemical toxicology 2004-06, Vol.42 (6), p.869-878
Hauptverfasser: Moonen, Harald J.J., Moonen, Edwin J.C., Maas, Lou, Dallinga, Jan W., Kleinjans, Jos C.S., de Kok, Theo M.C.M.
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container_issue 6
container_start_page 869
container_title Food and chemical toxicology
container_volume 42
creator Moonen, Harald J.J.
Moonen, Edwin J.C.
Maas, Lou
Dallinga, Jan W.
Kleinjans, Jos C.S.
de Kok, Theo M.C.M.
description 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display polymorphic distribution in the human population and are thus believed to cause interindividual differences in cancer risk susceptibility. The present study investigated the influence of dietary exposure and CYP1A2 and NAT2 genotypes and phenotypes on differential urinary PhIP excretion levels in 71 human volunteers after consumption of either a high (7.4 ng/g) or low (1.7 ng/g) dose of PhIP. Urinary PhIP excretion levels were found to reflect recent dietary exposure levels, with average levels of 174% (high dose group) and 127% (low dose group), as compared to pre-feed levels. Urinary caffeine metabolite ratios were significantly different between the two NAT2 genotypes, whereas for CYP1A2, the apparent difference in metabolic ratios between the genotypes was statistically non-significant. Significant correlations were firstly found between the CYP1A2-164A→C (CYP1A2*1F) polymorphism and differential urinary PhIP excretion levels. Although the found correlations are driven primarily by a small number of subjects possessing the homozygous variant constellation, the strong influence of this genotype indicates that the CYP1A2*1F polymorphism could play an important role in human cancer risk susceptibility.
doi_str_mv 10.1016/j.fct.2004.01.010
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Although the found correlations are driven primarily by a small number of subjects possessing the homozygous variant constellation, the strong influence of this genotype indicates that the CYP1A2*1F polymorphism could play an important role in human cancer risk susceptibility.</abstract><cop>Oxford</cop><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>15110095</pmid><doi>10.1016/j.fct.2004.01.010</doi><tpages>10</tpages></addata></record>
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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects acyltransferases
Administration, Oral
Adolescent
Adult
aromatic amines
Arylamine N-Acetyltransferase - genetics
Arylamine N-Acetyltransferase - pharmacology
Biological and medical sciences
biomarkers
carcinogenesis
carcinogens
Carcinogens - administration & dosage
Carcinogens - pharmacokinetics
Cooking
CYP1A21F polymorphism
cytochrome P-450
Cytochrome P-450 CYP1A2 - genetics
Cytochrome P-450 CYP1A2 - pharmacology
Cytochrome P4501A2
Diet
dose response
Female
food intake
genetic polymorphism
Genetic Predisposition to Disease
Genotype
heterocyclic amines
Heterocyclic aromatic amines
Humans
Imidazoles - administration & dosage
Imidazoles - urine
Medical sciences
metabolic studies
mutagenesis
N-acetyltransferase
neoplasms
nutrition-genotype interaction
Phenotype
Polymorphism, Genetic
Risk Factors
Toxicology
Urinary PhIP excretion
urination
volunteers
title CYP1A2 and NAT2 genotype/phenotype relations and urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in a human dietary intervention study
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