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⁻¹ 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.

为了了解银纳米颗粒（AgNPs）和银离子在肝脏中引起的遗传毒性，在这项研究中使用了工程化的金纳米棒核心/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 ^-1 Au @ Ag NR引起的DNA氧化应激和细胞周期停滞以及染色体损伤。此外，分析了Au @ Ag NR的分布。我们的研究结果表明，Ag ⁺和Au @ Ag NR都导致HepaRG细胞中的DNA裂解和染色体损伤（致死性），并且保留在细胞核中的Au @ Ag NR可能进一步释放Ag ⁺，加剧损伤，这主要是由于细胞周期停滞和ROS形成引起的。结果揭示了细胞内积累，Ag ⁺离子释放与AgNPs潜在的遗传毒性之间的相关性。