You are here:
GENE PROFILING IN WILD-TYPE AND PPARα-NULL MICE EXPOSED TO PERFLUOROOCTANE SULFONATE
Citation:
ROSEN, M. B., C. J. CORTON, J. E. SCHMID, R. ZEHR, K. DAS, H. REN, B. D. ABBOTT, AND C. LAU. GENE PROFILING IN WILD-TYPE AND PPARα-NULL MICE EXPOSED TO PERFLUOROOCTANE SULFONATE . Presented at 2009 SOT Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
To presented at 2009 SOT Annual Meeting
Description:
Perfluorooctane sulfonate (PFOS), a perfluoroalkyl acid (PFAA), is a persistent environmental contaminant found in the tissues of humans and wildlife. Over the last decade, health concerns have been raised, in part, because of the long half-life of PFOS and other PFAAs in humans, although serum levels of PFOS have begun to decrease since its phase out in 2002 by its major manufacturer. PFOS is a weak activator of peroxisome proliferator-activated receptor-alpha (PPARα) and exhibits hepatocarcinogenic potential in rats. PFOS is also a developmental toxicant in rodents, where differences have been observed between its mode of action and that of perfluorooctanoic acid (PFOA), a related PFAA. Wild-type (WT) and PPARα-null (KO) mice were dosed by oral gavage with PFOS (3 or 10 mg/kg/day), or vehicle for 7 days. Animals were euthanized, livers weighed, and liver samples collected for preparation of total RNA. Gene profiling was conducted on 5 mice per group using Affymetrix 430_2 GeneChips. In WT mice, PFOS induced changes characteristic of PPARα activation including regulation of genes associated with fatty acid metabolism, peroxisome biosynthesis, and proteasome biogenesis. The expression of PPARα marker genes such as Cyp4a14, Ehhadh, and Pdk4 was up-regulated. In KO mice, PFOS altered the expression of a subset of genes related to lipid metabolism and, in contrast to data previously evaluated for PFOA, induced unique changes to genes associated with oxidative phosphorylation/electron transport and cholesterol biosynthesis. The constitutive androstane receptor (CAR) marker gene, Cyp2b10, was up-regulated across all treatment groups while Cyp7a1, a gene known to be regulated by liver X receptor (LXR) and retinoid X receptor (RXR), was up-regulated only in KO mice. These data suggest that PFOS may have the potential to activate nuclear receptors other than PPARα, such as CAR, LXR, or RXRα. This abstract does not necessarily reflect EPA policy.