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HEPATIC GENE EXPRESSION PROFILES OF RATS EXPOSED TO PERFLUOROOCTANE SULFONATE (PFOS) IN UTERO
Citation:
Bjork, J., J. Berthiaume, C S. Lau, J. L. Butenhoff, AND K. B. Wallace. HEPATIC GENE EXPRESSION PROFILES OF RATS EXPOSED TO PERFLUOROOCTANE SULFONATE (PFOS) IN UTERO. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Hepatic Gene Expression Profiles of Rats Exposed to Perfluorooctanesulfonate (PFOS) in utero.
J.A. Bjork1, J.M. Berthiaume1, C. Lau2, J. L. Butenhoff3, and K.B. Wallace1
1Department of Biochemistry & Molecular Biology, University of Minnesota School of Medicine, Duluth, MN
2Reproductive Toxicology Division, NHEERL, US EPA, Research Triangle Park, NC
33M Company, St. Paul, MN
Perfluorooctanesulfonate (PFOS) is a surfactant that occurs primarily as a degradation product of some materials used for oil and water resistance. PFOS is persistent and widely dispersed in the environment. Toxicity testing indicates that PFOS interferes with intermediary metabolism by inducing the proliferation of peroxisomal bodies via transactivation of PPAR-a, both in adult and neonatal rodent species. The purpose of this investigation was to assess whether the observed modulation of lipid and fatty acid metabolism in liver of exposed neonates is reflected at the transcriptional level. Gravid Sprague-Dawley rats were exposed by gavage to 3 mg/kg PFOS/K+ beginning on gestational day (GD) 2. On GD21, liver was harvested from fetuses for RNA extraction and cRNA was generated for hybridization to Affymetrix 230A chips. Raw intensities were adjusted for background and normalized by the robust multichip analysis method. Statistical analysis revealed treatment-related differences in the degree of expression of 153 genes between the control and PFOS exposed animals (91 upregulated and 62 downregulated, p<0.01). The most prominent changes were the increased expression of both lipid synthesis and degradation pathways, as well as mitochondrial and peroxisomal b-oxidation genes, with no change in expression of the mitochondrial electron transport chain genes. On average, there was a two-fold induction of genes related to metabolism. The results of this investigation are in good concordance with previous observed changes in metabolic enzyme activity and intermediate profiles in rodents, suggesting that the metabolic effects associated with in uteroPFOS exposure inrodents are manifested at the transcriptional level and likely are related to PPAR-a activation.Supported by 3M Company. This abstract does not reflect EPA policy.