Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults

Maria Skaalum Petersen, Jónrit Halling, Per Damkier, Flemming Nielsen, Philippe Grandjean, Pál Weihe, Kim Brosen

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)202-206
Number of pages5
JournalTOXICOLOGY AND APPLIED PHARMACOLOGY
Volume224
Issue number2
DOIs
Publication statusPublished - 14 Jul 2007

Keywords

  • CYP3A4
  • 6 beta-hydroxycortisol/cortisol ratio
  • polychlorinated biphenyls
  • persistent organohalogen pollutants
  • Faroe islands
  • URINARY 6-BETA-HYDROXYCORTISOL
  • CYTOCHROME-P-450 ENZYMES
  • DRUG-INTERACTIONS
  • FREE CORTISOL
  • ISLANDS
  • HUMANS
  • POPULATION
  • GENDER
  • VARIABILITY
  • METABOLISM
  • Faroese

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