PMID- 17956617
OWN - NLM
STAT- MEDLINE
DCOM- 20080125
LR  - 20221207
IS  - 1476-069X (Electronic)
IS  - 1476-069X (Linking)
VI  - 6
DP  - 2007 Oct 23
TI  - AhR transcriptional activity in serum of Inuits across Greenlandic districts.
PG  - 32
AB  - 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. CONCLUSION: 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.
FAU - Long, Manhai
AU  - Long M
AD  - Unit of Cellular and Molecular Toxicology, Department of Environmental and 
      Occupational Medicine, Institute of Public Health, University of Aarhus, Denmark. 
      ml@mil.au.dk
FAU - Deutch, Bente
AU  - Deutch B
FAU - Bonefeld-Jorgensen, Eva C
AU  - Bonefeld-Jorgensen EC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071023
PL  - England
TA  - Environ Health
JT  - Environmental health : a global access science source
JID - 101147645
RN  - 0 (Benzofurans)
RN  - 0 (Dibenzofurans, Polychlorinated)
RN  - 0 (Dioxins)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Benzofurans/blood/pharmacology
MH  - Cell Line, Tumor
MH  - Dibenzofurans, Polychlorinated
MH  - Dioxins/blood/*pharmacology
MH  - Environmental Exposure/*analysis
MH  - Environmental Monitoring/methods
MH  - Environmental Pollutants/blood/*pharmacology
MH  - Feeding Behavior
MH  - Female
MH  - Food Chain
MH  - Greenland
MH  - Humans
MH  - Inuit/*ethnology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Polychlorinated Biphenyls/blood/pharmacology
MH  - Polychlorinated Dibenzodioxins/analogs & derivatives/blood/pharmacology
MH  - Receptors, Aryl Hydrocarbon/*drug effects/metabolism
PMC - PMC2173889
EDAT- 2007/10/25 09:00
MHDA- 2008/01/26 09:00
PMCR- 2007/10/23
CRDT- 2007/10/25 09:00
PHST- 2006/12/13 00:00 [received]
PHST- 2007/10/23 00:00 [accepted]
PHST- 2007/10/25 09:00 [pubmed]
PHST- 2008/01/26 09:00 [medline]
PHST- 2007/10/25 09:00 [entrez]
PHST- 2007/10/23 00:00 [pmc-release]
AID - 1476-069X-6-32 [pii]
AID - 10.1186/1476-069X-6-32 [doi]
PST - epublish
SO  - Environ Health. 2007 Oct 23;6:32. doi: 10.1186/1476-069X-6-32.