CBET Research Group, Dept. Zoology and Animal Cell Biology, Faculty of Science and Technology, Research Centre for Experimental Marine Biology and Biotechnology PIE, University of the Basque Country UPV/EHU, Basque Country, Spain.
Lung Cell Biology, Airway Disease, National Heart and Lung Institute, Imperial College London, London, UK.
Toxicol In Vitro. 2018 Apr;48:146-158. doi: 10.1016/j.tiv.2018.01.013.
There is a need to assess human and ecosystem health effects of copper oxide nanoparticles (CuO NPs), extensively used in many industrial products. Here, we aimed to determine the cytotoxicity and cellular mechanisms involved in the toxicity of CuO NPs in mussel cells (hemocytes and gill cells) in parallel with exposures to ionic Cu and bulk CuO, and to compare the sensitivity of mussel primary cells with a well-established human cell line (pulmonary TT1 cells). At similar doses, CuO NPs promoted dose-dependent cytotoxicity and increased reactive oxygen species (ROS) production in mussel and human cells. In mussel cells, ionic Cu was more toxic than CuO NPs and the latter more than bulk CuO. Ionic Cu and CuO NPs increased catalase and acid phosphatase activities in both mussel cells and decreased gill cells Na-K-ATPase activity. All Cu forms produced DNA damage in hemocytes, whereas in gill cells only ionic Cu and CuO NPs were genotoxic. Induction of the MXR transport activity was found in gill cells exposed to all forms of Cu and in hemocytes exposed to ionic Cu and CuO NPs. Phagocytosis increased only in hemocytes exposed to CuO NPs, indicating a nanoparticle-specific immunostimulatory effect. In conclusion, toxicity of CuO NPs is driven by ROS in human and mussel cells. Mussel cells respond to CuO NP exposure by triggering an array of defensive mechanisms.
需要评估氧化铜纳米颗粒（CuO NPs）对人类和生态系统健康的影响，因为它们被广泛应用于许多工业产品中。在这里，我们旨在确定 CuO NPs 在贻贝细胞（血细胞和鳃细胞）中的细胞毒性及其相关的细胞毒性机制，同时研究离子态 Cu 和块状 CuO 的暴露情况，并比较贻贝原代细胞与一种成熟的人类细胞系（肺 TT1 细胞）的敏感性。在相似的剂量下，CuO NPs 促进了贻贝和人类细胞的剂量依赖性细胞毒性和活性氧（ROS）的产生。在贻贝细胞中，离子态 Cu 的毒性大于 CuO NPs，而 CuO NPs 的毒性大于块状 CuO。离子态 Cu 和 CuO NPs 增加了贻贝细胞和鳃细胞中的过氧化氢酶和酸性磷酸酶的活性，降低了鳃细胞的 Na-K-ATPase 活性。所有 Cu 形态都在血细胞中产生了 DNA 损伤，而在鳃细胞中只有离子态 Cu 和 CuO NPs 具有遗传毒性。所有 Cu 形式都诱导了 gill 细胞中的 MXR 转运活性，而在血细胞中仅诱导了离子态 Cu 和 CuO NPs 的 MXR 转运活性。只有在血细胞中暴露于 CuO NPs 时，吞噬作用才会增加，这表明存在纳米颗粒特异性的免疫刺激作用。总之，CuO NPs 的毒性是由人类和贻贝细胞中的 ROS 驱动的。贻贝细胞通过触发一系列防御机制来应对 CuO NP 的暴露。
