Transactivation Potencies of the Baikal Seal {Pusa sibirica) Peroxisome Proliferator-Activated Receptor a by Perfluoroalkyl Carboxylates and Sulfonates: Estimation of PFOA Induction Equivalency Factors

摘要

The present study assessed the transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome prolif-erator-activated receptor a (BS PPARa) 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 /aM concentration, eight perfluoroalkyl carboxylates (PFCAs) and two perfluoroalkyl sulfonates (PFSAs) induced BS PPARa-mediated transcriptional activities in a dose-dependent manner. To compare the BS PPARa transactivation potencies of PFCs, the present study estimated the PFOA induction equivalency factors (lEFs), 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: l) > PFHpA (0.89) > PFNA (0.61) > PFPeA (0.50) > PFHxS (0.4l) > 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 PPARa. The analysis also indicated that PFCAs were more potent than PFSAs with the same number of perfluorinated carbons. Treatment with a mixture often PFCs showed an additive action on the BS PPARa 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 snowed 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 PPARa-mediated biological effects of complex mixtures of PFCs in wild Baikal seal population.