title: AhR transcriptional activity in serum of Inuits across Greenlandic districts.
abstract: BACKGROUND
  Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.
  
  
  METHODS
  The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.
  
  
  RESULTS
  In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk > or = Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.
  
  
  CONCLUSIONS
  i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.
authors.affiliation: Unit of Cellular and Molecular Toxicology, Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Denmark. ml@mil.au.dk
authors.forename: Manhai
authors.initials: M
authors.lastname: Long
authors.forename: Bente
authors.initials: B
authors.lastname: Deutch
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jorgensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001572:Benzofurans / Q000097:blood / Q000494:pharmacology; D045744:Cell Line, Tumor; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins / Q000097:blood / Q000494:pharmacology*; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring / Q000379:methods; D004785:Environmental Pollutants / Q000097:blood / Q000494:pharmacology*; D005247:Feeding Behavior; D005260:Female; D020387:Food Chain; D006116:Greenland; D006801:Humans; D004930:Inuit / Q000208:ethnology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls