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

Authors

  • Jason M. O'Brien,

    Corresponding author
    1. Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
    2. Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario, Canada
    • Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
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  • Aislynn J. Austin,

    1. Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
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  • Andrew Williams,

    1. Environmental Health Sciences and Research Bureau, Health Canada, Ottawa, Ontario, Canada
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  • Carole L. Yauk,

    1. Environmental Health Sciences and Research Bureau, Health Canada, Ottawa, Ontario, Canada
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  • Doug Crump,

    1. Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario, Canada
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  • Sean W. Kennedy

    1. Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
    2. Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario, Canada
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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. Environ. Toxicol. Chem. 2011;30:2846–2859. © 2011 SETAC

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