Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Environ Mol Mutagen. 2012 Jul;53(6):409-19. doi: 10.1002/em.21698. Epub 2012 May 10.
Silver nanoparticles (Ag-NPs) have increasingly been used for coatings on various textiles and certain implants, for the treatment of wounds and burns, as a water disinfectant, and in air-freshener sprays. The wide use of Ag-NPs may have potential human health impacts. In this study, the mutagenicity of 5-nm Ag-NPs was evaluated in the mouse lymphoma assay system, and modes of action were assessed using standard alkaline and enzyme-modified Comet assays and gene expression analysis. Treatments of L5178Y/Tk(+/-) mouse lymphoma cells with 5-nm uncoated Ag-NPs resulted in a significant yield of mutants at doses between 3 and 6 μg/mL; the upper range was limited by toxicity. Loss of heterozygosity analysis of the Tk mutants revealed that treatments with uncoated Ag-NPs induced mainly chromosomal alterations spanning less than 34 megabase pairs on chromosome 11. Although no significant induction of DNA damage in Ag-NP-treated mouse lymphoma cells was observed in the standard Comet assay, the Ag-NP treatments induced a dose-responsive increase in oxidative DNA damage in the enzyme-modified Comet assay in which oxidative lesion-specific endonucleases were added. Gene expression analysis using an oxidative stress and antioxidant defense polymerase chain reaction (PCR) array showed that the expressions of 17 of the 59 genes on the arrays were altered in the cells treated with Ag-NPs. These genes are involved in production of reactive oxygen species, oxidative stress response, antioxidants, oxygen transporters, and DNA repair. These results suggest that 5 nm Ag-NPs are mutagenic in mouse lymphoma cells due to induction of oxidative stress by the Ag-NPs.
银纳米粒子（Ag-NPs）已越来越多地用于各种纺织品和某些植入物的涂层，用于治疗伤口和烧伤，作为水消毒剂，并用于空气清新剂喷雾。Ag-NPs 的广泛使用可能对人类健康产生潜在影响。在这项研究中，使用小鼠淋巴瘤检测系统评估了 5nm Ag-NPs 的致突变性，并使用标准碱性和酶修饰彗星检测法以及基因表达分析评估了作用模式。用 5nm 未涂层的 Ag-NPs 处理 L5178Y/Tk(+/-) 小鼠淋巴瘤细胞，在 3 至 6μg/mL 之间的剂量下导致明显的突变体产生；上限受毒性限制。Tk 突变体的杂合性丧失分析表明，未涂层的 Ag-NPs 处理主要诱导了染色体 11 上小于 34 兆碱基对的染色体改变。虽然在标准彗星检测法中未观察到 Ag-NP 处理的小鼠淋巴瘤细胞中 DNA 损伤的显著诱导，但 Ag-NP 处理在添加氧化损伤特异性内切酶的酶修饰彗星检测法中诱导了氧化 DNA 损伤的剂量反应性增加。使用氧化应激和抗氧化防御聚合酶链反应（PCR）阵列进行的基因表达分析表明，Ag-NPs 处理的细胞中 59 个基因阵列上的 17 个基因的表达发生了改变。这些基因涉及活性氧物质的产生、氧化应激反应、抗氧化剂、氧气转运蛋白和 DNA 修复。这些结果表明，5nm Ag-NPs 由于 Ag-NPs 诱导的氧化应激而导致小鼠淋巴瘤细胞发生突变。
