Nguyen Kathy C, Richards Laura, Massarsky Andrey, Moon Thomas W, Tayabali Azam F
Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, HECSB, Health Canada, Ottawa, Ontario, Canada.
University of Ottawa, Department of Biology and Centre for Advanced Research in Environmental Genomics, Ottawa, Ontario, Canada.
Toxicol In Vitro. 2016 Jun;33:163-73. doi: 10.1016/j.tiv.2016.03.004. Epub 2016 Mar 11.
Silver nanoparticles (Ag-NPs) are highly relevant for human and environmental exposure due to their widespread use in consumer and medical products and various applications. Thus, there is a need for evaluating potential toxicity of these NPs. The objective of this study was to investigate the toxic effects of the OECD (Organization for Economic Co-operation and Development) representative Ag-NPs, NM300K, in mouse macrophage J774A.1 and human colonic epithelial HT29 cells, using multiple endpoint assays. Exposure of test cells to different concentrations (1-250 μg/mL; total silver content) of NM300K for 24h showed a dose-dependent decrease in cell viability. At high doses, NM300K altered cell shape and induced the formation of vacuolar structures, as examined by confocal and electron microscopy. Moreover, NM300K induced inflammation as evidenced by the elevated levels of pro-inflammatory cytokines. Finally, high doses of NM300K led to increased production of reactive oxygen species and induction of oxidative stress, leading to oxidative DNA damage and apoptosis in test cells. At equivalent silver concentrations, NM300K were less cytotoxic than AgNO3. However, the similar patterns in the effects of NM300K and AgNO3 throughout the assessed toxicological endpoints suggest that Ag(+) released from these NPs by dissolution could be a primary contributor to toxicity. This study is among the first to characterize the potential toxicity of OECD representative AgNPs in vitro, and provides additional insight into the biological mechanisms associated with Ag-NP toxicity.
由于银纳米颗粒（Ag-NPs）在消费品和医疗产品中广泛使用以及各种应用，它们与人类和环境暴露高度相关。因此，需要评估这些纳米颗粒的潜在毒性。本研究的目的是使用多种终点测定法，研究经合组织（经济合作与发展组织）代表性的Ag-NPs即NM300K对小鼠巨噬细胞J774A.1和人结肠上皮HT29细胞的毒性作用。将测试细胞暴露于不同浓度（1-250μg/mL；总银含量）的NM300K中24小时，结果显示细胞活力呈剂量依赖性下降。高剂量时，通过共聚焦显微镜和电子显微镜检查发现，NM300K改变了细胞形状并诱导形成了液泡结构。此外，促炎细胞因子水平升高证明NM300K诱导了炎症。最后，高剂量的NM300K导致活性氧生成增加并诱导氧化应激，从而导致测试细胞中的氧化性DNA损伤和凋亡。在银浓度相等时，NM300K的细胞毒性低于AgNO3。然而，在整个评估的毒理学终点中，NM300K和AgNO3的作用模式相似，这表明这些纳米颗粒通过溶解释放的Ag(+)可能是毒性的主要贡献者。本研究是最早对经合组织代表性银纳米颗粒的潜在毒性进行体外表征的研究之一，并为与银纳米颗粒毒性相关的生物学机制提供了更多见解。
