Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
Environ Sci Technol. 2011 Apr 1;45(7):3123-30. doi: 10.1021/es103748s. Epub 2011 Mar 7.
The present study assessed the transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α (BS PPARα) 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 μM concentration, eight perfluoroalkyl carboxylates (PFCAs) and two perfluoroalkyl sulfonates (PFSAs) induced BS PPARα-mediated transcriptional activities in a dose-dependent manner. To compare the BS PPARα 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 PPARα. 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 PPARα 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 PPARα-mediated biological effects of complex mixtures of PFCs in wild Baikal seal population.
本研究使用体外报告基因检测，评估了具有不同碳链长度（C4-C12）的全氟化学品（PFCs）对贝加尔海豹（Pusa sibirica）过氧化物酶体增殖物激活受体α（BS PPARα）的反式激活能力。在浓度范围为 7.8-250 μM 的 12 种 PFC 处理中，八种全氟烷基羧酸（PFCAs）和两种全氟烷基磺酸盐（PFSAs）以剂量依赖性方式诱导了 BS PPARα 介导的转录活性。为了比较 PFCs 对 BS PPARα 的反式激活能力，本研究估算了全氟辛酸的诱导等效因子（IEFs），即全氟辛酸的 50%有效浓度与每种化合物的浓度之比，该化合物能诱导与全氟辛酸的最大反应的 50%相对应的反应。PFCs 的 IEF 顺序如下：全氟辛酸（IEF：1）>全氟己酸（0.89）>全氟壬酸（0.61）>全氟庚酸（0.50）>全氟己基磺酸（0.41）>全氟辛酸（0.38）≈全氟癸酸（0.37）>全氟丁酸（0.26）=全氟辛烷磺酸（0.26）>全氟十一烷酸（0.15）≫全氟十二烷酸和全氟丁基磺酸（未激活）。结构-活性关系分析表明，具有超过七个全氟化碳的 PFCAs 与 PFCAs 的 IEF 之间存在负相关关系（r=-1.0，p=0.017），表明 PFCAs 的全氟化碳数是决定 BS PPARα 反式激活能力的因素之一。分析还表明，具有相同全氟化碳原子数的 PFCAs 比 PFSAs 更有效。十种 PFC 的混合物处理对 BS PPARα 激活表现出相加作用。使用个体 PFC 的 IEF 和野生贝加尔海豹肝脏中的 PFC 浓度，计算了全氟辛酸诱导当量（IEQs，5.3-58 ng IEQ/g 湿重）。相关性分析表明，肝脏总 IEQs 与肝脏细胞色素 P450 4A 样蛋白表达水平呈显著正相关（r=0.53，p=0.036）。这表明，我们的方法可能有助于评估野生贝加尔海豹种群中 PFC 复杂混合物对潜在 PPARα 介导的生物学效应。
