Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
Environ Toxicol Chem. 2011 Dec;30(12):2846-59. doi: 10.1002/etc.700.
Recently it was discovered that the perfluorooctane sulfonate (PFOS) detected in wildlife, such as fish-eating birds, had a greater proportion of linear PFOS (L-PFOS) than the manufactured technical product (T-PFOS), which contains linear and branched isomers. This suggests toxicological studies based on T-PFOS data may inaccurately assess exposure risk to wildlife. To determine whether PFOS effects were influenced by isomer content, we compared the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either L-PFOS or T-PFOS using Agilent microarrays. At equal concentrations (10 µM), T-PFOS altered the expression of more transcripts (340, >1.5-fold change, p < 0.05) compared with L-PFOS (130 transcripts). Higher concentrations of L-PFOS (40 µM) were also less transcriptionally disruptive (217 transcripts) than T-PFOS at 10 µM. Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, hepatic system development, and cellular growth and proliferation. Pathway and interactome analysis suggested that genes may be affected through the RXR receptor, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling, and PPARγ and SREBP receptors. In all functional categories and pathways examined, the response elicited by T-PFOS was greater than that of L-PFOS. These data show that T-PFOS elicits a greater transcriptional response in CEH than L-PFOS alone and demonstrates the importance of considering the isomer-specific toxicological properties of PFOS when assessing exposure risk.
最近发现，野生动物（如食鱼鸟类）体内检测到的全氟辛烷磺酸（PFOS）中，线性 PFOS（L-PFOS）的比例高于含有线性和支链异构体的制造技术产品（T-PFOS）。这表明，基于 T-PFOS 数据的毒理学研究可能无法准确评估野生动物的暴露风险。为了确定 PFOS 效应是否受到异构体含量的影响，我们使用 Agilent 微阵列比较了暴露于 L-PFOS 或 T-PFOS 的培养鸡胚肝细胞（CEH）的转录谱。在相同浓度（10 µM）下，T-PFOS 改变的转录本数量（340 个，>1.5 倍变化，p < 0.05）多于 L-PFOS（130 个转录本）。与 10 µM 的 T-PFOS 相比，较高浓度的 L-PFOS（40 µM）也较少引起转录扰乱（217 个转录本）。功能分析表明，L-PFOS 和 T-PFOS 影响参与脂质代谢、肝脏系统发育以及细胞生长和增殖的基因。通路和相互作用网络分析表明，基因可能通过 RXR 受体、氧化应激反应、TP53 信号通路、MYC 信号通路、Wnt/β-catenin 信号通路以及 PPARγ 和 SREBP 受体受到影响。在所检查的所有功能类别和通路中，T-PFOS 引起的反应大于 L-PFOS。这些数据表明，T-PFOS 在 CEH 中引起的转录反应大于单独的 L-PFOS，并证明在评估暴露风险时考虑 PFOS 的异构体特异性毒理学特性非常重要。
