Mao Zhenxing, Xia Wei, Wang Jun, Chen Tian, Zeng Qianqian, Xu Bing, Li Weiyong, Chen Xi, Xu Shunqing
Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Appl Toxicol. 2013 Nov;33(11):1268-76. doi: 10.1002/jat.2785. Epub 2012 Sep 13.
Perfluorooctane sulfonate (PFOS) is a widespread environmental contaminant that is detected in the lung of mammals. The mechanisms underlying PFOS-induced lung cytotoxicity remain unclear. The main purpose of this study was to evaluate the cytotoxic effects of PFOS on human lung cancer A549 cells and its possible molecular mechanism. A549 cells were treated with PFOS (0, 25, 50, 100 and 200 μm) and the cellular apoptosis, mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In this study, PFOS induced a dose-dependent increase in A549 cell toxicity via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3 and -9, and increased ratio of Bax/bcl-2 mRNA expression. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, can effectively block PFOS-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicate that PFOS induces apoptosis in A549 cells through a reactive oxygen species-mediated mitochondrial dysfunction pathway mechanism.
全氟辛烷磺酸（PFOS）是一种广泛存在的环境污染物，在哺乳动物的肺部可检测到。PFOS诱导肺细胞毒性的潜在机制仍不清楚。本研究的主要目的是评估PFOS对人肺癌A549细胞的细胞毒性作用及其可能的分子机制。用PFOS（0、25、50、100和200μM）处理A549细胞，并测定细胞凋亡、线粒体膜电位以及细胞内活性氧。在本研究中，PFOS通过凋亡途径诱导A549细胞毒性呈剂量依赖性增加，其特征为亚G1期百分比增加、caspase-3和-9激活以及Bax/bcl-2 mRNA表达比值增加。此外，存在明显的氧化应激，表现为谷胱甘肽水平降低、丙二醛水平升高和超氧化物歧化酶活性增加。N-乙酰半胱氨酸作为一种抗氧化剂，是一种直接的活性氧清除剂，可有效阻断PFOS诱导的活性氧生成、线粒体膜电位丧失和细胞凋亡。这些数据表明，PFOS通过活性氧介导的线粒体功能障碍途径机制诱导A549细胞凋亡。
