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HEPATIC GENE EXPRESSION PROFILING IN PERFLUOROHEXANE SULFONATE-EXPOSED WILD-TYPE AND PPARα-NULL MICE.
Citation:
ROSEN, M. B., J. E. SCHMID, K. DAS, H. REN, B. D. ABBOTT, AND C. LAU. HEPATIC GENE EXPRESSION PROFILING IN PERFLUOROHEXANE SULFONATE-EXPOSED WILD-TYPE AND PPARα-NULL MICE. Presented at Society of Toxicology (SOT) Annual meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
These results demonstrate that the influence of PFHxS on the murine transcriptone does not deviate significantly from that observed for other PFAAs and that PFHxS has both PPARα-dependent and -independent activity.
Description:
Perfluorohexane sulfonate (PFHxS) is one member of a group ofperfluoroakyl acids (PFAAs) presently recognized as widespread environmental contaminants. Like other PFAAs, PFHxS is also commonly found in human serum. Although PFHxS is presumed to be an activator of peroxisome proliferator-activated receptor-alpha (PPARα), little is known about its toxicity. Male wild-type (WT) and PPARα-null (Null) mice were dosed by oral gavage with PFHxS (3 or 10 mg/kg/day), or vehicle for 7 days. Animals were euthanized, livers weighed, and liver samples collected for preparation oftotal RNA. Gene profiling was conducted on 4 mice per group using Affymetrix 430_2 broad expression microarrays and the results were contrasted to data previously collected by our laboratory for other PFAAs. In WT mice, exposure to PFHxS altered the expression of genes associated with a number of PPARα-regulated biological functions including fatty acid metabolism, inflammation, peroxisome biogenesis, and proteasome biogenesis. Genes related to cholesterol biosynthesis were up-regulated in WT mice as well. In Null mice, changes induced by PFHxS reinforced findings from prior studies which indicated that in the absence of PPARa signaling, certain PFAAs maintain regulation of genes related to fatty acid metabolism such as Cyp4a14 and a various peroxisomal genes. The constitutive androstane receptor (CAR)-regulated gene, Cyp2blO, was up-regulated in both WT and Null mice suggesting that, as with various other PFAAs, PFHxS is an inducer of CAR. These results demonstrate that the influence of PFHxS on the murine transcriptone does not deviate significantly from that observed for other PFAAs and that PFHxS has both PPARα-dependent and -independent activity. (This abstract does not necessarily reflect EPA policy.)