Roles of ROS and cell cycle arrest in the genotoxicity induced by gold nanorod core/silver shell nanostructure.

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.