Polychlorinated Biphenyl (PCB) Induction of CYP3A4 Enzyme Activity in Healthy Faroese Adults

Details

• Personal Author:
  Brosen K ; Damkier P ; Grandjean P ; Halling J ; Nielsen F ; Petersen MS ; Weihe P
• 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 6beta-hydroxycortisol/cortisol (6beta-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6beta-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6beta-OHC/FC ratio than men (p=0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6beta-OHC/FC ratios and summation PCB, PCB-TEQ and p,p'-DDE, o,p'-DDT and HCB, respectively, but the associations were statistically significant for men only. [Description provided by NIOSH]
• Subjects:
  Aging Blood Energy Metabolism Environmental Exposure Environmental Pollution Enzymes Genetics Hematologic Tests Lipids Men Occupational Health Polychlorinated Biphenyls Risk Assessment Risk Factors Safety Urine Women

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• Keywords:
  6beta-Hydroxycortisol-cortisol Ratio Age Groups Author Keywords: CYP3A4 Blood Sampling DDT Dichlorodiphenyltrichloroethane Drugs Environmental Pollution Exposure Levels Faroe Islands Health Effects Humans Metabolism PCBs Persistent Organohalogen Pollutants Pharmacology Polychlorinated Biphenyls Risk Factors Urinalysis

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• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  202-206
• Volume:
  224
• Issue:
  2
• NIOSHTIC Number:
  nn:20059207
• Citation:
  Toxicol Appl Pharmacol 2007 Oct; 224(2):202-206
• Contact Point Address:
  Maria Skaalum Petersen, Institute of Public Health, Environmental Medicine, University of Southern Denmark, Winsløvparken 17, 5000 Odense C, Denmark
• Email:
  mskaalum@health.sdu.dk
• CAS Registry Number:
  1,1′-Biphenyl, chloro derivs. (CAS RN 1336-36-3)
• Federal Fiscal Year:
  2008
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4931a21c014d9b539196306d4c1277ea570b9e5772eb48715d5810f5b8691c837bc768690184fe4931cd2d0de448ac37a02fcdb5e6aac2decb79da1069235241
• Download URL:
  https://stacks.cdc.gov/view/cdc/223497/cdc_223497_DS1.pdf
• File Type:
  [PDF - 159.23 KB ]