Mutagenicity of PFOA in mammalian cells: role of mitochondria-dependent reactive oxygen species.
Mutagenicity of PFOA in mammalian cells: role of mitochondria-dependent reactive oxygen species.
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DOI：
10.1021/es1026129
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发表时间：
2011-02
影响因子：
11.4
通讯作者：
Guoping Zhao;Jun Wang;Xiaofei Wang;Shaopeng Chen;Ye Zhao;Feng Gu;A. Xu;Lijun Wu
中科院分区：
文献类型：
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作者：
Guoping Zhao;Jun Wang;Xiaofei Wang;Shaopeng Chen;Ye Zhao;Feng Gu;A. Xu;Lijun Wu
致突变性通常是恶性肿瘤发展的先决条件。有证据表明，暴露于全氟辛酸（PFOA）导致各种癌症诱发。然而，是否存在任何致突变基础仍然令人困惑。在本研究中，我们将指数生长的AL细胞暴露于PFOA，并测定细胞的存活率、突变诱导和caspase-3/7、-9活性。用线粒体DNA缺陷的人-仓鼠杂交细胞（ρ（0）AL）和活性氧（ROS）抑制剂来阐明其可能的机制。结果表明，PFOA处理AL细胞16天后，引起细胞内ROS、O2（.-）和一氧化氮（NO）水平，而处理ρ（0）AL细胞没有太大的变化。用ROS抑制剂同时处理AL细胞可显著降低PFOA的致突变性。此外，半胱天冬酶活性在AL细胞增加PFOA暴露和抑制ROS/RNS（活性氧/氮）抑制剂。我们的研究结果表明，暴露于PFOA导致AL细胞的致突变诱导，并在此过程中起着重要的作用，依赖于ROS。这为PFOA介导的癌症诱导提供了直接基础。
Mutagenicity is often a prerequisite to the development of malignancy. Evidences have shown that exposure to perfluorooctanoic acid (PFOA) results in various cancer inductions. However, whether any mutagenic base exists is still puzzling. In the present study, we exposed exponentially growing AL cells to PFOA and assayed the cells for survival, mutation induction, and caspase-3/7, -9 activities. Mitochondrial-DNA deficient human-hamster hybrid (ρ(0) AL) cells and reactive oxygen species (ROS) inhibitor were used to elucidate the possible mechanism. Our results showed that treatment of AL cells with PFOA for 16 days induced significant mutagenic effects together with the increment of ROS, superoxide anions (O2(.-)), and nitrogen oxide (NO) levels, while treatment of ρ(0) AL cells did not have much change. Concurrent treatment of AL cells with ROS inhibitor significantly decreased the mutagenic potential of PFOA. In addition, caspase activities in AL cells were increased by PFOA exposure and suppressed by ROS/RNS (reactive oxygen/nitrogen species) inhibitors. Our results suggest that exposure to PFOA lead to mutagenicity induction in AL cells, and mitochondria-dependent ROS plays an important role in this process. This provides a direct base for PFOA mediated cancer induction.