Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene
The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the gen...
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description | The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7
mg/m
3) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites. |
doi_str_mv | 10.1016/j.toxlet.2009.01.011 |
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mg/m
3) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.</description><identifier>ISSN: 0378-4274</identifier><identifier>EISSN: 1879-3169</identifier><identifier>DOI: 10.1016/j.toxlet.2009.01.011</identifier><identifier>PMID: 20117323</identifier><identifier>CODEN: TOLED5</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Adult ; Biological and medical sciences ; Blood ; Buccal swab ; Chemical and industrial products toxicology. Toxic occupational diseases ; Cytochrome P-450 CYP2E1 - genetics ; Cytochrome P-450 CYP2E1 - metabolism ; Cytochrome P450 2E1 ; Enzymes ; Excretion ; Genotype ; Glyoxylates - metabolism ; Glyoxylates - urine ; Human ; Humans ; Male ; Mandelic Acids - metabolism ; Mandelic Acids - urine ; Medical sciences ; Metabolites ; Middle Aged ; Occupational ; Occupational Exposure - analysis ; Phenotype ; Polymorphism ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphisms ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - chemistry ; RNA, Messenger - genetics ; Solvents ; Statistics, Nonparametric ; Styrene ; Styrene - pharmacokinetics ; Styrenes ; Toxicology ; Young Adult</subject><ispartof>Toxicology letters, 2010-01, Vol.192 (1), p.34-39</ispartof><rights>2009 Elsevier Ireland Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2009 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-685c971ed2a21b129c0e077c907f9fabad32029f7c1bcd07962da877ee246ab83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378427409000216$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,776,780,785,786,3537,23909,23910,25118,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22408955$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20117323$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Prieto-Castelló, M.J.</creatorcontrib><creatorcontrib>Cardona, A.</creatorcontrib><creatorcontrib>Marhuenda, D.</creatorcontrib><creatorcontrib>Roel, J.M.</creatorcontrib><creatorcontrib>Corno, A.</creatorcontrib><title>Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene</title><title>Toxicology letters</title><addtitle>Toxicol Lett</addtitle><description>The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7
mg/m
3) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Buccal swab</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Cytochrome P-450 CYP2E1 - genetics</subject><subject>Cytochrome P-450 CYP2E1 - metabolism</subject><subject>Cytochrome P450 2E1</subject><subject>Enzymes</subject><subject>Excretion</subject><subject>Genotype</subject><subject>Glyoxylates - metabolism</subject><subject>Glyoxylates - urine</subject><subject>Human</subject><subject>Humans</subject><subject>Male</subject><subject>Mandelic Acids - metabolism</subject><subject>Mandelic Acids - urine</subject><subject>Medical sciences</subject><subject>Metabolites</subject><subject>Middle Aged</subject><subject>Occupational</subject><subject>Occupational Exposure - analysis</subject><subject>Phenotype</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Polymorphisms</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - chemistry</subject><subject>RNA, Messenger - genetics</subject><subject>Solvents</subject><subject>Statistics, Nonparametric</subject><subject>Styrene</subject><subject>Styrene - pharmacokinetics</subject><subject>Styrenes</subject><subject>Toxicology</subject><subject>Young Adult</subject><issn>0378-4274</issn><issn>1879-3169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EomnhHyC0F0QvG8YfsdcXpCoqH1IlONADJ8vrnU0dbdaL7UXNv8dpUrgVaSTL8vPOjN-XkDcUlhSo_LBd5nA_YF4yAL0EWoo-IwvaKF1zKvVzsgCumlowJc7IeUpbAJBCrl6SM1ZYxRlfkO1twir0Vb7Dav3zO7um1QbHkPcTVnbsqunu8daH-EC1Pgxh450dql0YfQ7Rj5tDi-DcPNnsw1ie8H4KaY5Y5VClvI844ivyordDwten84Lcfrr-sf5S33z7_HV9dVM7sZK5ls3KaUWxY5bRljLtAEEpp0H1uret7TgDpnvlaOs6UFqyzjZKITIhbdvwC_L-2HeK4deMKZudTw6HwY4Y5mSUEJJyWK3-T3IuqZKCFfLySbL4zThXooGCiiPqYkgpYm-m6Hc27g0Fc0jObM0xOXNIzgAtRYvs7WnC3O6w-yt6jKoA706ATcX8PtrR-fSPYwIa_fCpj0cOi8e_PUaTnMfRYecjumy64J_e5A_Nkrjo</recordid><startdate>20100115</startdate><enddate>20100115</enddate><creator>Prieto-Castelló, M.J.</creator><creator>Cardona, A.</creator><creator>Marhuenda, D.</creator><creator>Roel, J.M.</creator><creator>Corno, A.</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><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>8FD</scope><scope>FR3</scope><scope>KR7</scope><scope>7X8</scope><scope>7ST</scope><scope>7T2</scope><scope>7U2</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope></search><sort><creationdate>20100115</creationdate><title>Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene</title><author>Prieto-Castelló, M.J. ; Cardona, A. ; Marhuenda, D. ; Roel, J.M. ; Corno, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-685c971ed2a21b129c0e077c907f9fabad32029f7c1bcd07962da877ee246ab83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Buccal swab</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Cytochrome P-450 CYP2E1 - genetics</topic><topic>Cytochrome P-450 CYP2E1 - metabolism</topic><topic>Cytochrome P450 2E1</topic><topic>Enzymes</topic><topic>Excretion</topic><topic>Genotype</topic><topic>Glyoxylates - metabolism</topic><topic>Glyoxylates - urine</topic><topic>Human</topic><topic>Humans</topic><topic>Male</topic><topic>Mandelic Acids - metabolism</topic><topic>Mandelic Acids - urine</topic><topic>Medical sciences</topic><topic>Metabolites</topic><topic>Middle Aged</topic><topic>Occupational</topic><topic>Occupational Exposure - analysis</topic><topic>Phenotype</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Polymorphisms</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - chemistry</topic><topic>RNA, Messenger - genetics</topic><topic>Solvents</topic><topic>Statistics, Nonparametric</topic><topic>Styrene</topic><topic>Styrene - pharmacokinetics</topic><topic>Styrenes</topic><topic>Toxicology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Prieto-Castelló, M.J.</creatorcontrib><creatorcontrib>Cardona, A.</creatorcontrib><creatorcontrib>Marhuenda, D.</creatorcontrib><creatorcontrib>Roel, J.M.</creatorcontrib><creatorcontrib>Corno, A.</creatorcontrib><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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Environment Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>Toxicology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Prieto-Castelló, M.J.</au><au>Cardona, A.</au><au>Marhuenda, D.</au><au>Roel, J.M.</au><au>Corno, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene</atitle><jtitle>Toxicology letters</jtitle><addtitle>Toxicol Lett</addtitle><date>2010-01-15</date><risdate>2010</risdate><volume>192</volume><issue>1</issue><spage>34</spage><epage>39</epage><pages>34-39</pages><issn>0378-4274</issn><eissn>1879-3169</eissn><coden>TOLED5</coden><abstract>The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7
mg/m
3) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>20117323</pmid><doi>10.1016/j.toxlet.2009.01.011</doi><tpages>6</tpages></addata></record> |
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subjects | Adult Biological and medical sciences Blood Buccal swab Chemical and industrial products toxicology. Toxic occupational diseases Cytochrome P-450 CYP2E1 - genetics Cytochrome P-450 CYP2E1 - metabolism Cytochrome P450 2E1 Enzymes Excretion Genotype Glyoxylates - metabolism Glyoxylates - urine Human Humans Male Mandelic Acids - metabolism Mandelic Acids - urine Medical sciences Metabolites Middle Aged Occupational Occupational Exposure - analysis Phenotype Polymorphism Polymorphism, Genetic Polymorphism, Restriction Fragment Length Polymorphisms Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - chemistry RNA, Messenger - genetics Solvents Statistics, Nonparametric Styrene Styrene - pharmacokinetics Styrenes Toxicology Young Adult |
title | Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene |
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