Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Mutat Res. 2012 Jun 14;745(1-2):4-10. doi: 10.1016/j.mrgentox.2011.11.010. Epub 2011 Nov 26.
Silver nanoparticles (AgNPs) have antimicrobial properties, which have contributed to their widespread use in consumer products. A current issue regarding nanomaterials is the extent to which existing genotoxicity assays are useful for evaluating the risks associated with their use. In this study, the genotoxicity of 5 nm AgNPs was assessed using two standard genotoxicity assays, the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus assay. Using the preincubation version of the Ames assay, Salmonella strains TA102, TA100, TA1537, TA98, and TA1535 were treated with 0.15-76.8 μg/plate of the AgNPs. Toxicity limited the doses that could be assayed to 2.4-38.4 μg/plate; no increases in mutant frequency over the vehicle control were found for the concentrations that could be assayed. Human lymphoblastoid TK6 cells were treated with 10-30 μg/ml AgNPs, and additional cells were treated with water and 0.73 gy X-rays as vehicle and positive controls. Micronucleus frequency was increased by the AgNP treatment in a dose-dependent manner. At a concentration of 30 μg/ml (with 45.4% relative population doubling), AgNPs induced a significant, 3.17-fold increase with a net increase of 1.60% in micronucleus frequency over the vehicle control, a weak positive response by our criteria. These results demonstrate that the 5 nm AgNP are genotoxic in TK6 cells. Also, the data suggest that the in vitro micronucleus assay may be more appropriate than the Ames test for evaluating the genotoxicity of the AgNPs.
纳米银颗粒(AgNPs)具有抗菌特性,这使得它们在消费产品中得到了广泛的应用。目前纳米材料的一个问题是,现有的遗传毒性检测在多大程度上可用于评估其使用相关的风险。在这项研究中,使用两种标准遗传毒性检测方法,即沙门氏菌回复突变检测(Ames 试验)和体外微核试验,评估了 5nm AgNPs 的遗传毒性。使用 Ames 试验的预孵育版本,用 0.15-76.8μg/平板的 AgNPs 处理 TA102、TA100、TA1537、TA98 和 TA1535 五种沙门氏菌菌株。毒性限制了可检测的剂量至 2.4-38.4μg/平板;在可检测的浓度下,突变频率未超过载体对照。用 10-30μg/ml AgNPs 处理人淋巴母细胞 TK6 细胞,并对额外的细胞分别用水和 0.73gy X 射线作为载体和阳性对照进行处理。微核频率呈剂量依赖性增加。在 30μg/ml 的浓度下(相对群体倍增 45.4%),AgNPs 以 3.17 倍的显著剂量依赖性方式诱导微核频率增加,相对于载体对照,微核频率增加了 1.60%,根据我们的标准,这是一个微弱的阳性反应。这些结果表明,5nm AgNP 在 TK6 细胞中具有遗传毒性。此外,数据表明,体外微核试验可能比 Ames 试验更适合评估 AgNPs 的遗传毒性。