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Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults
The CYP3A4 enzyme is, along with other cytochrome P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-( o-chlorophenyl), 2-( p′-chlorophenyl)ethane ( o, p′-DDT) and 1...
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| Published in: | Toxicology and applied pharmacology 2007-10, Vol.224 (2), p.202-206 |
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| container_title | Toxicology and applied pharmacology |
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| creator | Petersen, Maria Skaalum Halling, Jónrit Damkier, Per Nielsen, Flemming Grandjean, Philippe Weihe, Pál Brøsen, Kim |
| description | The CYP3A4 enzyme is, along with other cytochrome
P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(
o-chlorophenyl), 2-(
p′-chlorophenyl)ethane (
o,
p′-DDT) and 1,1,-dichloro-2,2-bis (
p-chlorophenyl)ethene (
p,
p′
-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18–60 years, the CYP3A4 activity was determined based on the urinary 6β-hydroxycortisol/cortisol (6β-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6β-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6β-OHC/FC ratio than men (
p
=
0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6β-OHC/FC ratios and ∑PCB, PCB–TEQ and
p,
p′-DDE,
o,
p′-DDT and HCB, respectively, but the associations were statistically significant for men only. |
| doi_str_mv | 10.1016/j.taap.2007.07.002 |
| format | article |
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P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(
o-chlorophenyl), 2-(
p′-chlorophenyl)ethane (
o,
p′-DDT) and 1,1,-dichloro-2,2-bis (
p-chlorophenyl)ethene (
p,
p′
-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18–60 years, the CYP3A4 activity was determined based on the urinary 6β-hydroxycortisol/cortisol (6β-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6β-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6β-OHC/FC ratio than men (
p
=
0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6β-OHC/FC ratios and ∑PCB, PCB–TEQ and
p,
p′-DDE,
o,
p′-DDT and HCB, respectively, but the associations were statistically significant for men only.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2007.07.002</identifier><identifier>PMID: 17692354</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; 6β-Hydroxycortisol/cortisol ratio ; Adolescent ; Adult ; Biological and medical sciences ; CYP3A4 ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - drug effects ; Cytochrome P-450 Enzyme System - metabolism ; DDT ; DDT - blood ; DDT - pharmacology ; Dichlorodiphenyl Dichloroethylene - blood ; Dichlorodiphenyl Dichloroethylene - pharmacology ; Environmental Exposure ; Environmental Pollutants - blood ; Environmental Pollutants - pharmacology ; ENZYME ACTIVITY ; Enzyme Induction - drug effects ; ENZYMES ; ETHANE ; ETHYLENE ; Faroe Islands ; Female ; Genetics, Population ; Humans ; HYDROCORTISONE ; Hydrocortisone - analogs & derivatives ; Hydrocortisone - metabolism ; Hydrocortisone - urine ; Male ; Medical sciences ; METABOLISM ; Middle Aged ; Persistent organohalogen pollutants ; POLLUTANTS ; POLYCHLORINATED BIPHENYLS ; Polychlorinated Biphenyls - blood ; Polychlorinated Biphenyls - pharmacology ; Polymorphism, Genetic ; RECEPTORS ; REGRESSION ANALYSIS ; Sex Factors ; Toxicogenetics ; Toxicology</subject><ispartof>Toxicology and applied pharmacology, 2007-10, Vol.224 (2), p.202-206</ispartof><rights>2007 Elsevier Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-a7cf929f7fd4fe1806cb99b348b3f871d75c22d501d11032a8850cf62fd6903</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19163434$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17692354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/21077828$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Petersen, Maria Skaalum</creatorcontrib><creatorcontrib>Halling, Jónrit</creatorcontrib><creatorcontrib>Damkier, Per</creatorcontrib><creatorcontrib>Nielsen, Flemming</creatorcontrib><creatorcontrib>Grandjean, Philippe</creatorcontrib><creatorcontrib>Weihe, Pál</creatorcontrib><creatorcontrib>Brøsen, Kim</creatorcontrib><title>Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>The CYP3A4 enzyme is, along with other cytochrome
P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(
o-chlorophenyl), 2-(
p′-chlorophenyl)ethane (
o,
p′-DDT) and 1,1,-dichloro-2,2-bis (
p-chlorophenyl)ethene (
p,
p′
-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18–60 years, the CYP3A4 activity was determined based on the urinary 6β-hydroxycortisol/cortisol (6β-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6β-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6β-OHC/FC ratio than men (
p
=
0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6β-OHC/FC ratios and ∑PCB, PCB–TEQ and
p,
p′-DDE,
o,
p′-DDT and HCB, respectively, but the associations were statistically significant for men only.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>6β-Hydroxycortisol/cortisol ratio</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>CYP3A4</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - drug effects</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>DDT</subject><subject>DDT - blood</subject><subject>DDT - pharmacology</subject><subject>Dichlorodiphenyl Dichloroethylene - blood</subject><subject>Dichlorodiphenyl Dichloroethylene - pharmacology</subject><subject>Environmental Exposure</subject><subject>Environmental Pollutants - blood</subject><subject>Environmental Pollutants - pharmacology</subject><subject>ENZYME ACTIVITY</subject><subject>Enzyme Induction - drug effects</subject><subject>ENZYMES</subject><subject>ETHANE</subject><subject>ETHYLENE</subject><subject>Faroe Islands</subject><subject>Female</subject><subject>Genetics, Population</subject><subject>Humans</subject><subject>HYDROCORTISONE</subject><subject>Hydrocortisone - analogs & derivatives</subject><subject>Hydrocortisone - metabolism</subject><subject>Hydrocortisone - urine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>METABOLISM</subject><subject>Middle Aged</subject><subject>Persistent organohalogen pollutants</subject><subject>POLLUTANTS</subject><subject>POLYCHLORINATED BIPHENYLS</subject><subject>Polychlorinated Biphenyls - blood</subject><subject>Polychlorinated Biphenyls - pharmacology</subject><subject>Polymorphism, Genetic</subject><subject>RECEPTORS</subject><subject>REGRESSION ANALYSIS</subject><subject>Sex Factors</subject><subject>Toxicogenetics</subject><subject>Toxicology</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNp9kN1rFDEQwINY7LX6D_ggC6LYhz0nyX4FfKmHtYWCB_qgIIRsPtgce8k1yRbWv75Z7qBvwsDA5DeTmR9CbzGsMeDm826dhDisCUC7XgLIC7TCwJoSKKUv0QqgwiVA9_scXcS4AwBWVfgVOsdtwwitqxX6u_XjLIfRB-tE0qro7WHQbh6LT9vN16vCOjXJZL0rvCk2f7b0uiq0-zfvdSFy_dGmOTPFoMWYhrm4EcHrmN_UNKb4Gp0ZMUb95pQv0c-bb782t-X9j-93m-v7UtY1TaVopWGEmdaoymjcQSN7xnpadT01XYtVW0tCVA1YYQyUiK6rQZqGGNUwoJfo_XGqj8nyKG3ScpDeOS0TJxjatiNdpj4eqUPwD5OOie9tlHochdN-ipwAZXmbKoPkCMrgYwza8EOwexFmjoEv3vmOL9754p0vASQ3vTtNn_q9Vs8tJ9EZ-HACRJRiNEE4aeMzx3CT_164L0dOZ1-PVoflIO2kVjYs9yhv_7fHE19sn5g</recordid><startdate>20071015</startdate><enddate>20071015</enddate><creator>Petersen, Maria Skaalum</creator><creator>Halling, Jónrit</creator><creator>Damkier, Per</creator><creator>Nielsen, Flemming</creator><creator>Grandjean, Philippe</creator><creator>Weihe, Pál</creator><creator>Brøsen, Kim</creator><general>Elsevier Inc</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>7TV</scope><scope>7U7</scope><scope>C1K</scope><scope>OTOTI</scope></search><sort><creationdate>20071015</creationdate><title>Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults</title><author>Petersen, Maria Skaalum ; Halling, Jónrit ; Damkier, Per ; Nielsen, Flemming ; Grandjean, Philippe ; Weihe, Pál ; Brøsen, Kim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-a7cf929f7fd4fe1806cb99b348b3f871d75c22d501d11032a8850cf62fd6903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>6β-Hydroxycortisol/cortisol ratio</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>CYP3A4</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - drug effects</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>DDT</topic><topic>DDT - blood</topic><topic>DDT - pharmacology</topic><topic>Dichlorodiphenyl Dichloroethylene - blood</topic><topic>Dichlorodiphenyl Dichloroethylene - pharmacology</topic><topic>Environmental Exposure</topic><topic>Environmental Pollutants - blood</topic><topic>Environmental Pollutants - pharmacology</topic><topic>ENZYME ACTIVITY</topic><topic>Enzyme Induction - drug effects</topic><topic>ENZYMES</topic><topic>ETHANE</topic><topic>ETHYLENE</topic><topic>Faroe Islands</topic><topic>Female</topic><topic>Genetics, Population</topic><topic>Humans</topic><topic>HYDROCORTISONE</topic><topic>Hydrocortisone - analogs & derivatives</topic><topic>Hydrocortisone - metabolism</topic><topic>Hydrocortisone - urine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>METABOLISM</topic><topic>Middle Aged</topic><topic>Persistent organohalogen pollutants</topic><topic>POLLUTANTS</topic><topic>POLYCHLORINATED BIPHENYLS</topic><topic>Polychlorinated Biphenyls - blood</topic><topic>Polychlorinated Biphenyls - pharmacology</topic><topic>Polymorphism, Genetic</topic><topic>RECEPTORS</topic><topic>REGRESSION ANALYSIS</topic><topic>Sex Factors</topic><topic>Toxicogenetics</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petersen, Maria Skaalum</creatorcontrib><creatorcontrib>Halling, Jónrit</creatorcontrib><creatorcontrib>Damkier, Per</creatorcontrib><creatorcontrib>Nielsen, Flemming</creatorcontrib><creatorcontrib>Grandjean, Philippe</creatorcontrib><creatorcontrib>Weihe, Pál</creatorcontrib><creatorcontrib>Brøsen, Kim</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>Pollution Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petersen, Maria Skaalum</au><au>Halling, Jónrit</au><au>Damkier, Per</au><au>Nielsen, Flemming</au><au>Grandjean, Philippe</au><au>Weihe, Pál</au><au>Brøsen, Kim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2007-10-15</date><risdate>2007</risdate><volume>224</volume><issue>2</issue><spage>202</spage><epage>206</epage><pages>202-206</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>The CYP3A4 enzyme is, along with other cytochrome
P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(
o-chlorophenyl), 2-(
p′-chlorophenyl)ethane (
o,
p′-DDT) and 1,1,-dichloro-2,2-bis (
p-chlorophenyl)ethene (
p,
p′
-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18–60 years, the CYP3A4 activity was determined based on the urinary 6β-hydroxycortisol/cortisol (6β-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6β-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6β-OHC/FC ratio than men (
p
=
0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6β-OHC/FC ratios and ∑PCB, PCB–TEQ and
p,
p′-DDE,
o,
p′-DDT and HCB, respectively, but the associations were statistically significant for men only.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>17692354</pmid><doi>10.1016/j.taap.2007.07.002</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Toxicology and applied pharmacology, 2007-10, Vol.224 (2), p.202-206 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_osti_scitechconnect_21077828 |
| source | ScienceDirect Freedom Collection |
| subjects | 60 APPLIED LIFE SCIENCES 6β-Hydroxycortisol/cortisol ratio Adolescent Adult Biological and medical sciences CYP3A4 Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - drug effects Cytochrome P-450 Enzyme System - metabolism DDT DDT - blood DDT - pharmacology Dichlorodiphenyl Dichloroethylene - blood Dichlorodiphenyl Dichloroethylene - pharmacology Environmental Exposure Environmental Pollutants - blood Environmental Pollutants - pharmacology ENZYME ACTIVITY Enzyme Induction - drug effects ENZYMES ETHANE ETHYLENE Faroe Islands Female Genetics, Population Humans HYDROCORTISONE Hydrocortisone - analogs & derivatives Hydrocortisone - metabolism Hydrocortisone - urine Male Medical sciences METABOLISM Middle Aged Persistent organohalogen pollutants POLLUTANTS POLYCHLORINATED BIPHENYLS Polychlorinated Biphenyls - blood Polychlorinated Biphenyls - pharmacology Polymorphism, Genetic RECEPTORS REGRESSION ANALYSIS Sex Factors Toxicogenetics Toxicology |
| title | Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults |
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