Determinants of AhR-mediated transcriptional activity induced by plasma extracts from Nunavik Inuit adults

The exposure of Inuit people to polychlorinated biphenyls (PCBs) and chlorinated pesticides has been well characterised but little is known regarding their exposure to dioxin-like compounds, which induce toxic effects through binding to the aryl hydrocarbon receptor (AhR). In order to obtain a global measure of persistent organic pollutants in plasma that interact with this signalling pathway, we used a luciferase reporter gene assay to assess the AhR-mediated transcriptional activity elicited by plasma sample extracts from 874 Inuit adults who were recruited in the course of a prospective epidemiological study conducted in Nunavik (Québec, Canada). Several sociodemographic, anthropometric, dietary and lifestyle variables were considered as possible modulating factors of the AhR-mediated activity in multivariate statistical analyses. The geometric mean AhR-mediated activity expressed as 2,3,7,8-tetachlorodibenzo-p-dioxin equivalents was 8.9 pg g(-1) lipids (range: <5-144 pg g(-1) lipids). PCB-153 concentration measured by high-resolution gas chromatography-mass spectrometry was moderately correlated to AhR-mediated activity (Pearson's r=0.53, p<0.001). Multiple linear regression analyses revealed that age and omega-3 fatty acids in erythrocyte membranes (an index of marine food consumption) were positively associated with plasma AhR-mediated activity (p<0.001), whereas a negative association was noted with body fat mass (p=0.037). These results suggest that AhR-mediated transcriptional activity of Inuit plasma extracts is linked to their organochlorine body burden, most likely that of dioxin-like PCBs, polychlorinated dibenzo-p-dioxins and polychlorodibenzofurans. AhR-mediated transcriptional activity measures may prove useful in investigating possible associations between exposure to AhR agonists and adverse health effects in this indigenous population.