title: Determinants of AhR-mediated transcriptional activity induced by plasma extracts from Nunavik Inuit adults.
abstract: 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.
authors.affiliation: Axe de Recherche en Santé des Populations et Environnementale, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Université Laval, 2875 Boulevard Laurier, Québec, QC, Canada. marc.medehouenou@mail.com
authors.forename: Thierry C M
authors.initials: TC
authors.lastname: Medehouenou
authors.forename: Christian
authors.initials: C
authors.lastname: Larochelle
authors.forename: Pierre
authors.initials: P
authors.lastname: Dumas
authors.forename: Eric
authors.initials: E
authors.lastname: Dewailly
authors.forename: Pierre
authors.initials: P
authors.lastname: Ayotte
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis; D004147:Dioxins / Q000633:toxicity*; D004435:Eating; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring; D006801:Humans; D004930:Inuit; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000097:blood; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D017747:Seafood / Q000706:statistics & numerical data; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl