Wei Yanhong, Liu Yang, Wang Jianshe, Tao Yi, Dai Jiayin
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Toxicol Appl Pharmacol. 2008 Feb 1;226(3):285-97. doi: 10.1016/j.taap.2007.09.023. Epub 2007 Oct 4.
Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant that has been detected in a variety of terrestrial and aquatic organisms. To assess the effects of PFOA in fish and predict its potential mode of action, a toxicogenomic approach was applied to hepatic gene expression profile analysis in male and female rare minnows (Gobiocypris rarus) using a custom cDNA microarray containing 1773 unique genes. Rare minnows were treated with continuous flow-through exposure to PFOA at concentrations of 3, 10, and 30 mg/L for 28 days. Based on the observed histopathological changes, the livers from fish exposed to 10 mg/L PFOA were selected for further hepatic gene expression analysis. While 124 and 171 genes were significantly altered by PFOA in males and females, respectively, of which 43 genes were commonly regulated in both sexes. The affected genes are involved in multiple biological processes, including lipid metabolism and transport, hormone action, immune responses, and mitochondrial functions. PFOA exposure significantly suppressed genes involved in fatty acid biosynthesis and transport but induced genes associated with intracellular trafficking of cholesterol. Alterations in expression of genes associated with mitochondrial fatty acid beta-oxidation were only observed in female rare minnows. In addition, PFOA inhibited genes responsible for thyroid hormone biosynthesis and significantly induced estrogen-responsive genes. These findings implicate PFOA in endocrine disruption. This work contributes not only to the elucidation of the potential mode of toxicity of PFOA to aquatic organisms but also to the use of toxicogenomic approaches to address issues in environmental toxicology.
全氟辛酸（PFOA）是一种普遍存在的环境污染物，已在多种陆生和水生生物中被检测到。为了评估PFOA对鱼类的影响并预测其潜在作用模式，采用毒理基因组学方法，使用包含1773个独特基因的定制cDNA微阵列，对雄性和雌性稀有鮈鲫（Gobiocypris rarus）的肝脏基因表达谱进行分析。稀有鮈鲫以连续流加的方式暴露于浓度为3、10和30 mg/L的PFOA中，持续28天。基于观察到的组织病理学变化，选择暴露于10 mg/L PFOA的鱼的肝脏进行进一步的肝脏基因表达分析。虽然PFOA分别使雄性和雌性中的124个和171个基因发生显著改变，但其中有43个基因在两性中受到共同调控。受影响的基因涉及多个生物学过程，包括脂质代谢和转运、激素作用、免疫反应和线粒体功能。PFOA暴露显著抑制了参与脂肪酸生物合成和转运的基因，但诱导了与胆固醇细胞内运输相关的基因。仅在雌性稀有鮈鲫中观察到与线粒体脂肪酸β-氧化相关基因表达的改变。此外，PFOA抑制了负责甲状腺激素生物合成的基因，并显著诱导了雌激素反应基因。这些发现表明PFOA具有内分泌干扰作用。这项工作不仅有助于阐明PFOA对水生生物的潜在毒性作用模式，也有助于利用毒理基因组学方法解决环境毒理学中的问题。
