Wang Dan, Dan Mo, Ji Yinglu, Wu Xiaochun, Wang Xue, Wen Hairuo
Beijing Key Laboratory, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, 100176, People's Republic of China.
China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Nanoscale Res Lett. 2020 Dec 7;15(1):224. doi: 10.1186/s11671-020-03455-1.
To understand the genotoxicity induced in the liver by silver nanoparticles (AgNPs) and silver ions, an engineered gold nanorod core/silver shell nanostructure (Au@Ag NR) and humanized hepatocyte HepaRG cells were used in this study. The involvement of oxidative stress and cell cycle arrest in the DNA and chromosome damage induced by 0.4-20 µg mL Au@Ag NR were investigated by comet assay, γ-H2AX assay and micronucleus test. Further, the distribution of Au@Ag NR was analyzed. Our results demonstrated that both Ag and Au@Ag NR led to DNA cleavage and chromosome damage (clastogenicity) in HepaRG cells and that the Au@Ag NR retained in the nucleus may further release Ag, aggravating the damages, which are mainly caused by cell cycle arrest and ROS formation. The results reveal the correlation between the intracellular accumulation, Ag ion release and the potential genotoxicity of AgNPs.
为了解银纳米颗粒（AgNPs）和银离子在肝脏中诱导的遗传毒性，本研究使用了一种工程化的金纳米棒核/银壳纳米结构（Au@Ag NR）和人源化肝细胞HepaRG细胞。通过彗星试验、γ-H2AX试验和微核试验，研究了0.4-20 μg/mL Au@Ag NR诱导的氧化应激和细胞周期阻滞与DNA和染色体损伤的关系。此外，还分析了Au@Ag NR的分布。我们的结果表明，Ag和Au@Ag NR均可导致HepaRG细胞中的DNA断裂和染色体损伤（致断裂性），并且保留在细胞核中的Au@Ag NR可能会进一步释放Ag，加重损伤，这些损伤主要由细胞周期阻滞和ROS形成引起。结果揭示了细胞内积累、Ag离子释放与AgNPs潜在遗传毒性之间的相关性。
