Department of Zoology, National Food Safety and Toxicology Center and Institute of Environmental Toxicology, Michigan State University, East Lansing, 224 National Food Safety and Toxicology Center, MI 48824-1311, USA.
Environ Toxicol Pharmacol. 2005 Jan;19(1):57-70. doi: 10.1016/j.etap.2004.04.008.
Perfluorooctane sulfonic acid (PFOS) is widely distributed in the environment including in the tissues of wildlife and humans, however, its mechanism of action remains unclear. Here, the Affymetrix rat genome U34A genechip was used to identify alterations in gene expression due to PFOS exposure. Rat hepatoma cells were treated with PFOS at 2-50mg/L (4-100μM) for 96h. Sprague-Dawley rats were orally dosed with PFOS at 5mg/kg/day for 3 days or 3 weeks. Genes that were significantly (P <0.0025) induced were primarily genes for fatty acid metabolizing enzymes, cytochrome P450s, or genes involved in hormone regulation. Consistent expression profiles were obtained for replicate exposures, for short-term and long-term in vivo exposures, and for acute and chronic exposures. One major pathway affected by PFOS was peroxisomal fatty acid β-oxidation, which could be explained by the structural similarity between PFOS and endogenous fatty acids.
全氟辛烷磺酸（PFOS）广泛分布于环境中，包括野生动物和人类的组织中，但作用机制尚不清楚。本研究采用 Affymetrix 大鼠基因组 U34A 基因芯片，鉴定 PFOS 暴露导致的基因表达改变。用 2-50mg/L（4-100μM）PFOS 处理大鼠肝癌细胞 96 小时，用 5mg/kg/天 PFOS 灌胃染毒 Sprague-Dawley 大鼠 3 天或 3 周。基因芯片结果显示，差异表达的基因主要是脂肪酸代谢酶、细胞色素 P450s 或与激素调节相关的基因。重复暴露、短期和长期体内暴露以及急性和慢性暴露均获得了一致的表达谱。受 PFOS 影响的一个主要途径是过氧化物酶体脂肪酸β-氧化，这可以用 PFOS 与内源性脂肪酸的结构相似性来解释。
