Boyles Matthew S P, Ranninger Christina, Reischl Roland, Rurik Marc, Tessadri Richard, Kohlbacher Oliver, Duschl Albert, Huber Christian G
Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg, Hellbrunner Strasse 34, 5020, Salzburg, Austria.
Department of Molecular Biology, Division of Chemistry and Bioanalytics, University of Salzburg, Hellbrunner Strasse 34, 5020, Salzburg, Austria.
Part Fibre Toxicol. 2016 Sep 8;13(1):49. doi: 10.1186/s12989-016-0160-6.
The rapidly increasing number of engineered nanoparticles (NPs), and products containing NPs, raises concerns for human exposure and safety. With this increasing, and ever changing, catalogue of NPs it is becoming more difficult to adequately assess the toxic potential of new materials in a timely fashion. It is therefore important to develop methods which can provide high-throughput screening of biological responses. The use of omics technologies, including metabolomics, can play a vital role in this process by providing relatively fast, comprehensive, and cost-effective assessment of cellular responses. These techniques thus provide the opportunity to identify specific toxicity pathways and to generate hypotheses on how to reduce or abolish toxicity.
We have used untargeted metabolome analysis to determine differentially expressed metabolites in human lung epithelial cells (A549) exposed to copper oxide nanoparticles (CuO NPs). Toxicity hypotheses were then generated based on the affected pathways, and critically tested using more conventional biochemical and cellular assays. CuO NPs induced regulation of metabolites involved in oxidative stress, hypertonic stress, and apoptosis. The involvement of oxidative stress was clarified more easily than apoptosis, which involved control experiments to confirm specific metabolites that could be used as standard markers for apoptosis; based on this we tentatively propose methylnicotinamide as a generic metabolic marker for apoptosis.
Our findings are well aligned with the current literature on CuO NP toxicity. We thus believe that untargeted metabolomics profiling is a suitable tool for NP toxicity screening and hypothesis generation.
工程纳米颗粒（NPs）以及含有NPs的产品数量迅速增加，引发了对人类接触和安全性的担忧。随着NPs种类不断增加且不断变化，及时充分评估新材料的潜在毒性变得越来越困难。因此，开发能够提供生物反应高通量筛选的方法很重要。包括代谢组学在内的组学技术，通过对细胞反应提供相对快速、全面且经济高效的评估，可在这一过程中发挥至关重要的作用。这些技术因此提供了识别特定毒性途径并就如何降低或消除毒性提出假设的机会。
我们使用非靶向代谢组分析来确定暴露于氧化铜纳米颗粒（CuO NPs）的人肺上皮细胞（A549）中差异表达的代谢物。然后根据受影响的途径生成毒性假设，并使用更传统的生化和细胞试验进行严格测试。CuO NPs诱导了参与氧化应激、高渗应激和细胞凋亡的代谢物的调节。氧化应激的参与比细胞凋亡更容易阐明，细胞凋亡涉及对照实验以确认可作为细胞凋亡标准标志物的特定代谢物；基于此，我们初步提出甲基烟酰胺作为细胞凋亡的通用代谢标志物。
我们的研究结果与当前关于CuO NP毒性的文献高度一致。因此，我们认为非靶向代谢组学分析是NP毒性筛选和假设生成的合适工具。
