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 1,1,-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 3 10 randomly selected Faroese residents aged 18-60 years, the CYP3A4 activity was determined based on the urinary 6 beta-hydroxycortisol/cortisol (6 beta-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6 beta-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6 beta-OHC/ FC ratio than men (p=0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6 beta-OHC/FC ratios and Sigma PCB, PCB-TEQ and p,p'-DDE, o,p'-DDT and HCB, respectively, but the associations were statistically significant for men only. (C) 2007 Elsevier Inc. All rights reserved.