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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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 |
format | Article |
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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.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2004.01.010</identifier><identifier>PMID: 15110095</identifier><identifier>CODEN: FCTOD7</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>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</subject><ispartof>Food and chemical toxicology, 2004-06, Vol.42 (6), p.869-878</ispartof><rights>2004 Elsevier Ltd</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-ffde59be38ed38f3b227a758c7b44a2651d1d70c16661a84403bb93c2cd221433</citedby><cites>FETCH-LOGICAL-c434t-ffde59be38ed38f3b227a758c7b44a2651d1d70c16661a84403bb93c2cd221433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fct.2004.01.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15728155$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15110095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moonen, Harald J.J.</creatorcontrib><creatorcontrib>Moonen, Edwin J.C.</creatorcontrib><creatorcontrib>Maas, Lou</creatorcontrib><creatorcontrib>Dallinga, Jan W.</creatorcontrib><creatorcontrib>Kleinjans, Jos C.S.</creatorcontrib><creatorcontrib>de Kok, Theo M.C.M.</creatorcontrib><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</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><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.</description><subject>acyltransferases</subject><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Adult</subject><subject>aromatic amines</subject><subject>Arylamine N-Acetyltransferase - genetics</subject><subject>Arylamine N-Acetyltransferase - pharmacology</subject><subject>Biological and medical sciences</subject><subject>biomarkers</subject><subject>carcinogenesis</subject><subject>carcinogens</subject><subject>Carcinogens - administration & dosage</subject><subject>Carcinogens - pharmacokinetics</subject><subject>Cooking</subject><subject>CYP1A21F polymorphism</subject><subject>cytochrome P-450</subject><subject>Cytochrome P-450 CYP1A2 - genetics</subject><subject>Cytochrome P-450 CYP1A2 - pharmacology</subject><subject>Cytochrome P4501A2</subject><subject>Diet</subject><subject>dose response</subject><subject>Female</subject><subject>food intake</subject><subject>genetic polymorphism</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>heterocyclic amines</subject><subject>Heterocyclic aromatic amines</subject><subject>Humans</subject><subject>Imidazoles - administration & dosage</subject><subject>Imidazoles - urine</subject><subject>Medical sciences</subject><subject>metabolic studies</subject><subject>mutagenesis</subject><subject>N-acetyltransferase</subject><subject>neoplasms</subject><subject>nutrition-genotype interaction</subject><subject>Phenotype</subject><subject>Polymorphism, Genetic</subject><subject>Risk Factors</subject><subject>Toxicology</subject><subject>Urinary PhIP excretion</subject><subject>urination</subject><subject>volunteers</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2KFDEUhQtRnHb0AdxoNoqC6clNUj-Nq6bxZ2DQBmcWIhJSya3pDFWpNqkaLF_HFzU13aAr4UJC-M7h3JwsewpsCQyKs5tlY4YlZ0wuGaRh97IFVKWghcjhfrZgvKxosYL8JHsU4w1jrISyeJidQA7A2CpfZL83X7ew5kR7Sz6tLzm5Rt8P0x7P9rvjjQRs9eB6H--oMTivw0Twpwk4P5O-IZzqzvmeAu1w2E0tLeisn1rXOat_9d_km5yS-vt-Cs46j-TVdne-fU2cJ5rsxk57Yh0Os6_zA4Zb9HfWcRjt9Dh70Og24pPjeZpdvX93uflILz5_ON-sL6iRQg60aSzmqxpFhVZUjag5L3WZV6aspdS8yMGCLZmBoihAV1IyUdcrYbixnIMU4jR7efDdh_7HiHFQnYsG21Z77MeooFzJquAsgXAATehjDNiofXBdCq-AqbkZdaNSM2puRjFIM2ueHc3HukP7V3GsIgEvjoCORrdN0N64-A9X8grymXt-4BrdK30dEnP1hTMQySVtlstEvD0QmD7r1mFQ0Tj0Bq0LmGLZ3v0n6B-JSLT1</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Moonen, Harald J.J.</creator><creator>Moonen, Edwin J.C.</creator><creator>Maas, Lou</creator><creator>Dallinga, Jan W.</creator><creator>Kleinjans, Jos C.S.</creator><creator>de Kok, Theo M.C.M.</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20040601</creationdate><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</title><author>Moonen, Harald J.J. ; Moonen, Edwin J.C. ; Maas, Lou ; Dallinga, Jan W. ; Kleinjans, Jos C.S. ; de Kok, Theo M.C.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-ffde59be38ed38f3b227a758c7b44a2651d1d70c16661a84403bb93c2cd221433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>acyltransferases</topic><topic>Administration, Oral</topic><topic>Adolescent</topic><topic>Adult</topic><topic>aromatic amines</topic><topic>Arylamine N-Acetyltransferase - genetics</topic><topic>Arylamine N-Acetyltransferase - pharmacology</topic><topic>Biological and medical sciences</topic><topic>biomarkers</topic><topic>carcinogenesis</topic><topic>carcinogens</topic><topic>Carcinogens - administration & dosage</topic><topic>Carcinogens - pharmacokinetics</topic><topic>Cooking</topic><topic>CYP1A21F polymorphism</topic><topic>cytochrome P-450</topic><topic>Cytochrome P-450 CYP1A2 - genetics</topic><topic>Cytochrome P-450 CYP1A2 - pharmacology</topic><topic>Cytochrome P4501A2</topic><topic>Diet</topic><topic>dose response</topic><topic>Female</topic><topic>food intake</topic><topic>genetic polymorphism</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>heterocyclic amines</topic><topic>Heterocyclic aromatic amines</topic><topic>Humans</topic><topic>Imidazoles - administration & dosage</topic><topic>Imidazoles - urine</topic><topic>Medical sciences</topic><topic>metabolic studies</topic><topic>mutagenesis</topic><topic>N-acetyltransferase</topic><topic>neoplasms</topic><topic>nutrition-genotype interaction</topic><topic>Phenotype</topic><topic>Polymorphism, Genetic</topic><topic>Risk Factors</topic><topic>Toxicology</topic><topic>Urinary PhIP excretion</topic><topic>urination</topic><topic>volunteers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moonen, Harald J.J.</creatorcontrib><creatorcontrib>Moonen, Edwin J.C.</creatorcontrib><creatorcontrib>Maas, Lou</creatorcontrib><creatorcontrib>Dallinga, Jan W.</creatorcontrib><creatorcontrib>Kleinjans, Jos C.S.</creatorcontrib><creatorcontrib>de Kok, Theo M.C.M.</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moonen, Harald J.J.</au><au>Moonen, Edwin J.C.</au><au>Maas, Lou</au><au>Dallinga, Jan W.</au><au>Kleinjans, Jos C.S.</au><au>de Kok, Theo M.C.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>42</volume><issue>6</issue><spage>869</spage><epage>878</epage><pages>869-878</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><coden>FCTOD7</coden><abstract>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.</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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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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