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PERFLUOROPHOSPHONIC ACID ACTIVATES PEROXISOME PROUFERATOR-ACTIVATED RECEPTOR-ALPHA BUT NOT CONSTITUTIVE ANDROSTANE RECEPTOR IN THE MURINE LIVER
Citation:
DAS, K., P. Rosen, B. Mitchell, C. R. WOOD, B. D. ABBOTT, AND C. LAU. PERFLUOROPHOSPHONIC ACID ACTIVATES PEROXISOME PROUFERATOR-ACTIVATED RECEPTOR-ALPHA BUT NOT CONSTITUTIVE ANDROSTANE RECEPTOR IN THE MURINE LIVER. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
The current study was designed to evaluate liver toxicity of PFPAs and to contrast these findings to studies previously conducted by our group for other PFAAs. Two independent experiments were conducted
Description:
Masurf FS-780 is a commercial perfluoro-chemical mixture that contains C612-perfluoroalkylphosphonic acid (PFPA) derivatives. PFPAs have received recent attention as a previously under recognized subclass of perfluoroalkyl acids (PFAAs) that are found in the environment. The current study was designed to evaluate liver toxicity of PFPAs and to contrast these findings to studies previously conducted by our group for other PFAAs. Two independent experiments were conducted. In experiment one, adult male CD-1 mice were given Masurf FS-780 once daily for 7 days by oral gavage at 10.4. or 41.6 mglkg. In a second experiment, SV129 wild-type (WT) and peroxisome proliferator-activated receptor alpha (PPARa)-null male mice (Null) were similarly dosed with Masurf FS-780 at 3.1 or 20.8 mg/kg/day. Mice from each dose group, along with concurrent controls, were sacrificed 24 h after the last treatment. Liver samples were collected for real time RT-PCR of selected genes using Taqman assays. Dose-dependent elevations of liver weight were found in CD-1 and SV129 WT mice but not in Null mice. Similarly, genes known to be regulated by PPARa were up-regulated in a dose-dependent fashion in CD-1 and SV129 WT mice but, with the exception of Cyp4a14, were unchanged in Null mice. Hence, like other PFAAs, PFPAs appear to function as an activators of PPARa. Unlike other PFAAs (perfluorooctanoic acid, perfluorooctane sulfonate, perfluorononanoic acid), Masurf FS-780 does not up-regulate the constitutive androstane receptor (CAR) regulated gene, Cyp2b10, in either strain of mice examined suggesting that PFPAs may not activate CAR. These results suggest that PFPA-induced liver enlargement occurs specifically through activation of PPARa. (This abstract does not necessarily reflect US EPA policy.)