Caffeine N3-Demethylation (CYP1A2) in a Population with an Increased Exposure to Polychlorinated Biphenyls

Details

• Personal Author:
  Brosen K ; Damkier P ; Grandjean P ; Halling J ; Nielsen F ; Petersen MS ; Weihe P
• Description:
  Objective: To investigate the CYP1A2 phenotype distribution in a population with an increased exposure to polychlorinated biphenyls (PCBs) that would likely induce an increased activity of this enzyme. Further, to investigate the effect of sex, smoking, and oral contraceptive use on the CYP1A2 activity. Methods: In 305 randomly selected Faroese residents aged 18-60 years, the CYP1A2 activity was determined following oral intake of a caffeine dose and subsequent determination of the urinary metabolites and calculation of the caffeine metabolic ratio (CMR). PCB exposure was assessed by measuring the serum concentration of major congeners. Results: The CYP1A2 phenotype distribution was unimodal. The CMR was significantly higher both in smoking men and in smoking women, independent of oral contraceptive use, as compared with non-smokers. Among nonsmokers, the CMR was significantly higher in women not using oral contraceptives than in those using oral contraceptives; a similar difference could not be established among smokers. The CMR appeared higher in men than in women, but stratified analyses confirmed a significant sexrelated difference only among smokers not using oral contraceptives. Overall, the mean CMR in Faroese was significantly higher compared with the mean CMR in Danish historical controls. No association was found with PCB exposure and individual PCB congeners, except for one of three dioxin-like congeners, in confounder-adjusted multiple regression analyses. Conclusion: The CYP1A2 phenotype in Faroese residents was unimodally distributed and showed the inducing effect of smoking and the inhibiting effect of use of oral contraceptives, but a sex-related difference was not apparent after confounder adjustment. There was no statistically significant association between CMR and PCB exposure. [Description provided by NIOSH]
• Subjects:
  Aging Energy Metabolism Environmental Exposure Enzymes Men Occupational Health Polychlorinated Biphenyls Risk Assessment Risk Factors Safety Smokers Urine Women

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• Keywords:
  Age Groups Author Keywords: CYP1A2 Caffeine Caffeine Metabolic Ratio Exposure Levels Faroe Islands Humans Metabolites N3-demethylation PCBs Polychlorinated Biphenyls Risk Factors Smoking Urinalysis Urine Chemistry

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• ISSN:
  0031-6970
• 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
• Volume:
  62
• Issue:
  12
• NIOSHTIC Number:
  nn:20059208
• Citation:
  Eur J Clin Pharacol 2006 Dec; 62(12):1041-1048
• Contact Point Address:
  Maria Skaalum Petersen, Institute of Public Health, Department of Environmental Medicine, University of Southern Denmark, Winslovparken 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:
  2007
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  European Journal of Clinical Pharmacology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1d4eae49d50c66219f0564b594935e821f08c595cc63ab63be7bc21e4a149b6ae94dd7cca675db1dbc167b83f4cea54f83d0f0bfeb2e5918ed8d9a43ea24b9c3
• Download URL:
  https://stacks.cdc.gov/view/cdc/223498/cdc_223498_DS1.pdf
• File Type:
  [PDF - 194.86 KB ]