Technical‐grade perfluorooctane sulfonate alters the expression of more transcripts in cultured chicken embryonic hepatocytes than linear perfluorooctane sulfonate

Abstract

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.

Use of an avian hepatocyte assay and the avian toxchip polymerse chain reaction array for testing prioritization of 16 organic flame retardants

“…This family of enzymes plays an important role in lipid synthesis, fatty acid catabolism, and phospho‐lipid remodeling . 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase, the rate‐limiting enzyme in cholesterol biosynthesis that is regulated by hormonal factors, including cholesterol, thyroid hormone, and estradiol, was induced following PFOS exposure in CEH . Similar to the microarray study by Farhat et al (A. Farhat et al, Environment Canada, Ottawa, Ontario, Canada, unpublished manuscript) lipid metabolism was the top enriched functional category for differentially expressed genes , highlighting the susceptibility of this pathway to a diverse range of environmental contaminants both in vitro and in vivo.…”

Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo

“…In addition, retinoids can stimulate oligodendrocyte precursor cell differentiation and remyelination via RXR (Huang et al, 2011). The binding assays of Vanden Heuvel et al (2006), has shown that PFOS does not activate human, rat or mouse RXR; however PFOS has been shown to alter the expression of both PPARγ and RXR in chicken embryonic hepatocytes (O'Brien et al, 2011). The alteration in the differentiation process of NSCs that we observed in the current study may be linked by the complexity of PPARγ signaling due to the synergistic or non-synergistic outcome of PPAR/ RXR heterodimer and the DNA-binding dependent or independent mechanisms of PPARγ (as reviewed by Abdelrahman et al, 2005).…”

Perfluoroalkylated substances in food: occurrence and dietary exposure

“…Since the linear PFOS has a higher bioaccumulation potential (Chu et al, 2009;O'Brian et al, 2011) it can be assumed that the reported PFOS occurrence data mainly refers to the linear isomer. EFSA Journal 2012; 10(6):2743 Across foods of plant origin, PFOS was found in vegetables and wild edible fungi in concentrations from 0.0043 to 1.54 µg/kg, in fruits in concentrations from 0.003 to 0.54 µg/kg, in one potato sample (1.2 µg/kg) and in one bean sample (0.0063 µg/kg).…”