No effect of CYP1B1 Val432Leu polymorphism on CYP1B1 messenger RNA levels in an organochlorine-exposed population in Slovakia.

Cytochrome P450 1B1 (CYP1B1) is a phase I enzyme involved in the metabolic activation of many polycyclic aromatic hydrocarbons. It is also involved in the hydroxylation of estradiol to 4-hydroxyestradiol, a potentially genotoxic metabolite that is suggested to play a role in carcinogenesis. CYP1B1 is expressed in many tissues including mononuclear peripheral blood cells and is regulated through the aryl hydrocarbon receptor–mediated pathway, which can be induced by several environmental chemicals, including polycyclic aromatic hydrocarbons and persistent organochlorine pollutants such as polychlorinated biphenyls (PCB). A single nucleotide polymorphism of the CYP1B1 gene (1,294G!C) leads to an amino acid substitution in codon 432 (Val to Leu). This substitution results in a lower catalytic activity of the enzyme (1), but the effect of this CYP1B1 Val432Leu polymorphism on CYP1B1 gene expression and its inducibility is not clear. Gene expression and genotype of CYP1B1 can easily be determined in blood lymphocytes, making it a potential candidate to be used as biomarker for exposure to aryl hydrocarbon receptor agonists. We studied the correlation between CYP1B1 gene expression level and exposure to environmental factors within the CYP1B1 Val432Leu genotype groups. This study was part of a European project (PCBRISK) that investigates a human population exposed to environmental pollution as a consequence of the 25-year-long production of PCBs in eastern Slovakia.