Human exposure assessments for perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) have been mostly limited to the quantification of these chemicals in different environmental matrices, but only a few studies have addressed toxicological aspects associated with them. It has been suggested that both PFOA and PFOS are highly stable chemicals that are not metabolized, yet previous reports have described abnormal activity of important biotransformation pathways. Therefore, the goal of the present study was to investigate the effects of PFOA and PFOS on phase I and II biotransformation enzymes at the gene expression and activity levels, and by using the well-established human liver HepaRG cell line. Cells were exposed to a wide range of PFOA and PFOS concentrations for 24 or 48 h, prior to cytotoxicity measurements, and quantification of expression and activity of three cytochrome P450 enzymes (CYP1A2, CYP2C19 and CYP3A4) and two conjugation enzymes (glutathione-S-transferase (GST-M1) and UDP-glucuronosyltransferase (UGT-1A1)). Expression of all CYP enzymes was significantly reduced from exposure to both PFOA and PFOS after 48 h and from concentrations as low as 40-50 ng/L, with CYP3A4 also presenting the lowest activity. Among the conjugation enzymes, the expression of UGT was significantly reduced only by PFOA after 48 h of exposure, yet no significant alterations in its activity were observed. While the specific chemico-biological interactions of these compounds with gene expression and biotransformation pathways is not clear, the results from this study suggest that the interference of PFOA and PFOS with phase I and II biotransformation enzymes could potentially lead to adverse outcomes resulting from the inability of biotransformation pathways to function as needed.

中文翻译：

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全氟辛酸酯（PFOA）和全氟辛烷磺酸（PFOS）改变了人肝细胞中I和II期生物转化酶的表达和活性。

人类对全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）的暴露评估仅限于在不同环境基质中对这些化学物质进行定量分析，但只有少数研究解决了与它们相关的毒理学方面。有人提出，PFOA和PFOS都是高度稳定的化学物质，不会被代谢，但是以前的报道已经描述了重要生物转化途径的异常活性。因此，本研究的目的是通过使用成熟的人肝HepaRG细胞系，研究PFOA和PFOS在基因表达和活性水平上对I和II期生物转化酶的影响。在进行细胞毒性测量之前，将细胞暴露于各种PFOA和PFOS浓度下24或48 h，并定量三种细胞色素P450酶（CYP1A2，CYP2C19和CYP3A4）和两种结合酶（谷胱甘肽S-转移酶（GST-M1）和UDP-葡萄糖醛酸转移酶（UGT-1A1））的表达和活性。从暴露于PFOA和PFOS后48小时和从低至40-50 ng / L的浓度中，所有CYP酶的表达均显着降低，其中CYP3A4的活性也最低。在缀合酶中，UGT的表达仅在暴露48 h后被PFOA显着降低，但未观察到其活性的显着改变。尽管这些化合物与基因表达和生物转化途径之间的特定化学-生物学相互作用尚不清楚，