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首页> 外文期刊>Environmental toxicology and chemistry >Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line
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Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line

机译：整合细胞和分子终点以评估HepG2细胞系中多环芳烃的毒性

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Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effects of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr), and 3 halogenated derivatives of these compounds (1-chloropyrene, 1-bromopyrene [1-BrPyr], and 7-chlorobenzo[a]anthracene [7-ClBaA]) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h, except for multiple dose exposure to BaA and 7-ClBaA (1M/d for 4 d) and single exposure to 10M BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. To understand the underlying molecular mechanisms responsible for this effect, reactive oxygen species production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, and early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24h as measured by catalase activity, and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase, and MTT and neutral red assays. Evaluation of cell death mediators showed that caspase-3/7, but not annexin-V, pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential. Environ Toxicol Chem 2017;36:3404-3414. (c) 2017 SETAC
机译：多环芳烃（PAH）是存在于环境中的持久性污染物，具有已知的诱变和致癌特性。在本研究中，暴露于单剂量或多剂量的苯并[a]蒽（BaA），pyr（Pyr）和这些化合物的3种卤代衍生物（1-氯py，1-溴py [1-BrPyr]和在肝脏来源的人类细胞系（HepG2）中评估了7-氯苯并[a]蒽[7-ClBaA]。经典的3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）和中性红试验评估的细胞毒性显示，对单次或多次剂量暴露长达72h的反应具有中等毒性，除了多次暴露于BaA和7-ClBaA（1M / d，持续4 d）和一次暴露于10M BaA之外。此外，分别观察到Pyr和BaA系列的选择性线粒体和溶酶体毒性。为了了解引起这种作用的潜在分子机制，在暴露于单剂量化合物后，评估了活性氧的产生，线粒体膜的去极化，溶酶体的pH值，DNA断裂以及早期和晚期凋亡介体。通过过氧化氢酶活性测量，所有化合物均能够在24小时后触发氧化应激，并且线粒体膜去极化，溶酶体pH升高，MTT和中性红分析之间发现了良好的相关性。对细胞死亡介体的评估表明，caspase-3 / 7而不是膜联蛋白-V途径参与了由研究化合物触发的毒性反应。所有结果的综合表明1-BrPyr和BaA具有更高的毒性潜能。 Environ Toxicol Chem 2017; 36：3404-3414。 （c）2017年SETAC

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