Moratin Helena, Scherzad Agmal, Gehrke Thomas, Ickrath Pascal, Radeloff Katrin, Kleinsasser Norbert, Hackenberg Stephan
Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Wuerzburg, Germany.
Environ Mol Mutagen. 2018 Apr;59(3):247-259. doi: 10.1002/em.22156. Epub 2017 Nov 18.
The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells. Therefore, human head and neck squamous cell carcinoma-derived FaDu cells were incubated with 4-20 µg/ml of ZnO-NPs for 1-48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase-3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time- and dose-dependent effects. Human mesenchymal bone marrow stem cells were used as non-malignant representatives to examine oxidative stress-related genotoxicity. Results showed a significant reduction in cell viability as well as dose- and time-dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase-3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti-cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247-259, 2018. © 2017 Wiley Periodicals, Inc.
氧化锌纳米颗粒（ZnO-NPs）在工业应用以及消费品中的使用日益增加，这在更大程度上引发了人们对其潜在不利影响的担忧。众多研究已证明纳米颗粒具有毒性，但对于其潜在机制仍缺乏了解。本研究旨在系统地调查ZnO-NP诱导的细胞毒性、凋亡、细胞周期改变和遗传毒性。此外，该研究的目的还包括明确纳米颗粒暴露对恶性细胞与非恶性细胞的不同影响。因此，将人源头颈部鳞状细胞癌衍生的FaDu细胞与4-20μg/ml的ZnO-NPs孵育1-48小时，并就时间和剂量依赖性效应测试细胞活力、细胞周期改变、凋亡以及作为分子凋亡过程敏感标志物的caspase-3基因表达。将人间充质骨髓干细胞用作非恶性细胞代表，以检测氧化应激相关的遗传毒性。结果显示，纳米颗粒处理后细胞活力显著降低，凋亡细胞呈剂量和时间依赖性增加。同样，在首次检测到凋亡细胞之前，caspase-3基因表达就已增强。可以观察到，对肿瘤细胞具有细胞毒性的剂量并未降低干细胞的活力。然而，相同浓度已诱导出显著的DNA损伤。该研究结果表明，对于将纳米颗粒用作抗癌剂的做法应持更谨慎的态度。不过，还需要更多的体内研究来评估对消费者和患者的安全问题。《环境与分子突变》59:247-259，2018年。©2017威利期刊公司
