ToxSci Advance Access published online on October 17, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl135
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1 Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711
* To whom correspondence should be addressed. This study evaluates the potential for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) to activate peroxisome proliferator-activated receptors (PPARs), using a transient transfection cell assay. Cos-1 cells were cultured in DMEM with fetal bovine serum (FBS) in 96-well plates and transfected with mouse or human PPAR alpha ( Disclaimer: This paper has been reviewed by the National Health and Environmental Effects Research Laboratory, US EPA. Mention of trade names of commercial products does not constitute endorsement/recommendation for use.
Received September 21, 2006
Accepted October 11, 2006
In Vitro Toxicology
Activation of Mouse and Human Peroxisome Proliferator-Activated Receptors (PPAR
Margy L. Takacs 1 and Barbara D. Abbott 1 *
, 
/
, 
) by Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS)
Barbara D. Abbott, E-mail: abbott.barbara{at}epa.gov
Abstract 
), beta (
/
), or gamma (
) reporter plasmids. Transfected cells were exposed to PFOA (0.5-100 µM), PFOS (1-250 µM), positive controls (i.e. known agonists and antagonists), and negative controls (i.e. DMEM, 0.1% water, and 0.1% DMSO). Following treatment for 24 hours, 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 PPAR/ activity relative to vehicle. PFOS significantly increased activation of mouse PPAR and PPAR/ 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 , /, by PFOA and PFOS. While this model allows opportunities to compare potential activation by perfluoroalkyl acids (PFAAs), it only evaluates the interaction and activation of the PPAR reporter constructs and is not necessarily predictive of a toxicological response in vivo.
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