ToxSci Advance Access originally published online on October 17, 2006
Toxicological Sciences 2007 95(1):108-117; doi:10.1093/toxsci/kfl135
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Published by Oxford University Press 2006.
Activation of Mouse and Human Peroxisome Proliferator–Activated Receptors (
, ß/
, 
) by Perfluorooctanoic Acid and Perfluorooctane Sulfonate
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at NHEERL Building, US Environmental Protection Agency, 2525 East Highway 54, Durham, NC 27713. Fax: (919) 541-4017. Email abbott.barbara{at}epa.gov.
Received September 21, 2006; accepted October 11, 2006
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Abstract |
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This study evaluates the potential for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) to activate peroxisome proliferator–activated receptors (PPARs), using a transient transfection cell assay. Cos-1 cells were cultured in Dulbecco's Minimal Essential Medium (DMEM) with fetal bovine serum in 96-well plates and transfected with mouse or human PPAR
, ß/
, or 
reporter plasmids. Transfected cells were exposed to PFOA (0.5–100µM), PFOS (1–250µM), positive controls (i.e., known agonists and antagonists), and negative controls (i.e., DMEM, 0.1% water, and 0.1% dimethyl sulfoxide). Following treatment for 24 h, activity was measured using the Luciferase reporter assay. In this assay, PFOA had more transactivity than PFOS with both the mouse and human PPAR isoforms. PFOA significantly increased mouse and human PPAR and mouse PPARß/ activity relative to vehicle. PFOS significantly increased activation of mouse PPAR and PPARß/ isoforms. No significant activation of mouse or human PPAR was observed with PFOA or PFOS. The PPAR antagonist, MK-886, significantly suppressed PFOA and PFOS activity of mouse and human PPAR. The PPAR antagonist, GW9662, significantly suppressed PFOA activity on the human isoform. In conclusion, this study characterized the dose response and differential activation of mouse and human PPAR, ß/, by PFOA and PFOS. While this model allows opportunities to compare potential activation by perfluoroalkyl acids, it only evaluates the interaction and activation of the PPAR reporter constructs and is not necessarily predictive of a toxicological response in vivo.
Key Words: PPAR; PFOA; PFOS; transient transfection assay; Cos-1 cells.
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