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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-3-30
pubmed:abstractText
The present study assessed the transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor ? (BS PPAR?) by perfluorochemicals (PFCs) having various carbon chain lengths (C4-C12) using an in vitro reporter gene assay. Among the twelve PFCs treated with a range of 7.8-250 ?M concentration, eight perfluoroalkyl carboxylates (PFCAs) and two perfluoroalkyl sulfonates (PFSAs) induced BS PPAR?-mediated transcriptional activities in a dose-dependent manner. To compare the BS PPAR? transactivation potencies of PFCs, the present study estimated the PFOA induction equivalency factors (IEFs), a ratio of the 50% effective concentration of PFOA to the concentration of each compound that can induce the response corresponding to 50% of the maximal response of PFOA. The order of IEFs for the PFCs was as follows: PFOA (IEF: 1)>PFHpA (0.89)>PFNA (0.61)>PFPeA (0.50)>PFHxS (0.41)>PFHxA (0.38)?PFDA (0.37)>PFBA (0.26)=PFOS (0.26)>PFUnDA (0.15)?PFDoDA and PFBuS (not activated). The structure-activity relationship analysis showed that PFCAs having more than seven perfluorinated carbons had a negative correlation (r=-1.0, p=0.017) between the number of perfluorinated carbons and the IEF of PFCAs, indicating that the number of perfluorinated carbon of PFCAs is one of the factors determining the transactivation potencies of the BS PPAR?. The analysis also indicated that PFCAs were more potent than PFSAs with the same number of perfluorinated carbons. Treatment with a mixture of ten PFCs showed an additive action on the BS PPAR? activation. Using IEFs of individual PFCs and hepatic concentrations of PFCs in the liver of wild Baikal seals, the PFOA induction equivalents (IEQs, 5.3-58 ng IEQ/g wet weight) were calculated. The correlation analysis revealed that the hepatic total IEQs showed a significant positive correlation with the hepatic expression levels of cytochrome P450 4A-like protein (r=0.53, p=0.036). This suggests that our approach may be useful for assessing the potential PPAR?-mediated biological effects of complex mixtures of PFCs in wild Baikal seal population.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-5851
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3123-30
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor ? by perfluoroalkyl carboxylates and sulfonates: estimation of PFOA induction equivalency factors.
pubmed:affiliation
Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't