Title: Expression of CYP1A1 and 1B1 MRNA in blood lymphocytes from two district populations in Slovakia compared to total TEQS in blood as measures by the DRE-CALUX® ASSAY

Auteur(s): Canton RF ; Besselink HT ; Sanderson JT ; Botschuijver S ; Brouwer A ; Van den Berg M ;  ; 

Year: 2003

Journal: Organohalogen Compounds

Subject(s): CYP1A1 ; estrogen ; dioxins ; dioxin ; PCBs ; PCB ; dioxin-like compounds ; TCDD ; PAH ; Biomarkers ; Biomarker ; TEQ ; blood plasma ;  ; 

Summary: Cytochrome P450 lAl (CYP1A1) and 1B1 (CYP1B1) are members of the P450 1 family and are involved in the bioactivation of a broad range of xenobiotics and endogenous compounds such as estrogens. Induction of these enzymes has been associated with a various biological and toxicological responses, inc1uding carcinogenesis. Both genes are dioxin-inducible genes and are regulated by the aryl hydrocarbon receptor (AhR) which shows a high binding affinity for certain chlorinated dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs). The induction of these two enzymes is one of the more sensitive biological effects of dioxin-like compounds. Thus, the measurement of CYP1A1 and CYP1B1 in humans and wildlife is considered to be useful in establishing relationships between dioxin exposure and possible low-level adverse health effects. In vitro studies have demonstrated a dose-dependent induction of CYP1A1 and CYP1B1 (mRNA??) in human peripheral lymphocytes by TCDD (Spencer et al., 1999). This suggests the possibility of using CYP1A1 or CYP1B1 mRNA levels in blood cells as a biological marker of exposure of AhR ligands such as dioxins, PCBs and polycyc1ic aromatic hydrocarbons (PAHs). A recent study of Chinese coke oven workers indeed associated these CYP1A1 and 1B1 mRNA levels with elevated exposure to PAHs (Hanaoka et al., 2002). The objective of our present study was to quantify CYP1A1 and CYP1B1 mRNA levels in human lymphocytes from two different human populations in Slovakia. The blood samples were collected from an area that was highly PCB-polluted and one intended to represent background exposure in the rest of the country. We are presently evaluating the CYP1A1 and 1B1 mRNA levels in blood lymphocytes from these two populations as possible biomarkers of human exposure to dioxin and related compounds. We determined the mRNA levels of CYP1A1 and CYP1B1 by a quantitative reverse transcription-PCR method in these lymphocytes. In addition, we examined if there was an association between the individual level of CYP1A1 and 1B1 expression, which could be expected based on the similar mechanism of induction mediated via the AhR. We also examined a possible re1ationship between CYP1A1 and 1B1 mRNA levels and TEQs in blood plasma as determined using an Ah receptor-dependent reporter (DRE-CALUX) system.