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2E - Genomics, Proteonomics, Metabolomics (TUP/123) Identification of Genes Responsive to Perfluorooctane Sulfonic Acid Exposure Using Gene Expression Profiling. Giesy, John1, Hu, Wenyue1, Jones, Paul1, Newsted, John1, 2, Lau, Chris3, 1 Michigan State University, East Lansing, MI, USA2 Entrix Inc., East Lansing, MI, USA3 US-EPA, Research Triangle Park, North Carolina, USA ABSTRACT- Perfluorooctane sulfonic acid (PFOS) is the terminal metabolite of a number of perfluorinated fatty acid analogues extensively used in industrial materials and commercial applications and has become widely distributed in the environment, including the tissues of wildlife and humans. Few toxicological studies have been conducted on this compound, and its mechanism of action, if any, remains unclear. In the current study, the Affymetrix rat genome U34A gene chip was used to identify alterations in gene expression due to in vitro and in vivo PFOS exposure. H4IIE rat hepatoma cells were treated with solvent only or with PFOS at 2 or 50 mg/L for 96 hr. Sprague-Dawley rats were dosed via oral gavage with vehicle or PFOS at 5mg/kg/day for either 3 d or 3 wk. Genes that were significantly induced in response to PFOS exposure were primarily characterized as genes encoding fatty acid metabolizing enzymes, cytochrome P450s, or genes involved in hormone regulation. Genes encoding proteins involved in signal transduction pathways, and neurosystem regulation were among those whose expression levels were suppressed by PFOS exposure. Consistent gene expression profiles were obtained from replicate exposures. Expression profiles observed in vitro were significantly different from those expressed in vivo. Responses were similar for short-term and long-term in vivo exposures, which suggests that the biological effects were similar for acute and chronic exposure. The major target pathway of PFOS is postulated to be peroxisomal fatty acid beta-oxidation, the induction of which could be explained by the structural similarity between PFOS and endogenous fatty acids. Key words: GeneArray, PFOS, gene expression, metabolism |
