Genotoxic potential of the perfluorinated chemicals PFOA, PFOS, PFBS, PFNA and PFHxA in human HepG2 cells
Genotoxic potential of the perfluorinated chemicals PFOA, PFOS, PFBS, PFNA and PFHxA in human HepG2 cells
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DOI：
10.1016/j.mrgentox.2010.04.024
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发表时间：
2010-07-19
影响因子：
1.9
通讯作者：
Moller, Peter
中科院分区：
文献类型：
--
作者：
Eriksen, Kirsten Thorup;Raaschou-Nielsen, Ole;Moller, Peter
人工合成的全氟化学品（pfc）因其抗润湿和表面活性剂的特性而广泛应用于工业产品。全氟化合物被怀疑是致癌物，其作用机制可能是氧化应激的产生。我们研究了五种不同的pfc在HepG2细胞中产生活性氧（ROS）和诱导氧化性DNA损伤的潜力。全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）分别使细胞内ROS产量增加1.52倍（95% Cl, 1.37-1.67）和1.25倍（95% Cl, 1.10-1.40）。然而，ROS生成的增加不依赖于浓度，并且化合物不会产生DNA损伤，这些DNA损伤可以通过碱性彗星试验检测到，如链断裂和碱不稳定位点或甲脒嘧啶-DNA糖基化酶（FPG）位点。全氟丁烷磺酸（PFBS）和全氟己酸（PFHxA）不产生ROS或DNA损伤。只有暴露于全氟壬酸（PFNA）才会在细胞毒性浓度水平下引起DNA损伤的适度增加，这是通过乳酸脱氢酶（LDH）释放到细胞培养基中来检测的。这与ROS的产生无关。总的来说，这些结果表明，在代表人类肝脏的细胞系中，pfc在ROS产生和DNA损伤方面仅诱导适度的影响。(C) 2010 Elsevier B.V.版权所有
Synthetically produced perfluorinated chemicals (PFCs) are widely used in industrial products because of their anti-wetting and surfactant properties. PFCs are suspected carcinogens and a possible mechanism of action is generation of oxidative stress. We have investigated the potential of five different PFCs to generate reactive oxygen species (ROS) and to induce oxidative DNA damage in HepG2 cells. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) increased the intracellular ROS production by 1.52-fold (95% Cl, 1.37-1.67) and 1.25-fold (95% Cl, 1.10-1.40), respectively. However, the increase in ROS production was not concentration-dependent and the compounds did not generate DNA damage that could be detected by the alkaline comet assay as strand breakage and alkali-labile sites or formamidopyrimidine-DNA-glycosylase (FPG) sites. Perfluorobutane sulfonate (PFBS) and perfluorohexanoic acid (PFHxA) did not generate ROS or DNA damage. Only the exposure to perfluorononanoic acid (PFNA) caused a modest increase in DNA damage at a cytotoxic concentration level, which was detected as lactate dehydrogenase (LDH) release into the cell medium. This was not related to ROS generation. Collectively, these results indicate that PFCs induce only modest effects in terms of ROS production and DNA damage in a cell line representing the human liver. (C) 2010 Elsevier B.V. All rights reserved.