In recent years, increasing data have demonstrated that silver-nanoparticles (NPs) could induce toxicity in vivo under a variety of exposure conditions, and many in vitro investigations demonstrated that silver-NPs could cause strong cytotoxicity in a broad species of cells. Based on these toxicological investigations, the information and knowledge for understanding the toxicity of silver-NPs is increasing. Therefore, concerns about safety and clinical risks of the silver-NP-based medical products are being raised. In this study, genotoxicity of silver-NP-based hydrogel (silver-NP/Gel) was assayed by using cytokinesis-block micronucleus (CBMN), and the molecular response was demonstrated by using DNA microarray and GO pathway analysis. Silver-NP-based hydrogel induced the formation of micronuclei in HeLa cells (Table 1). The graphical abstract of working process for global gene expression analysis was showed in Figure 1. The global gene expression analysis suggested that fourteen theoretical activating signaling pathways were attributed to up-regulated genes, they mainly include cell communication, metabolic process, immune and transport pathway; and three signal pathways were attributed to down-regulated genes, they include nucleobase, nucleoside, nucleotide and nucleic acid metabolic processes, cell cycle and mitosis pathway at 48 h of silver-NP/Gel exposure in HeLa cells. It was further discussed that the changes of DNA damage, apoptosis and mitosis pathway related genes were closely related to silver-NP-induced cytotoxicity and chromosome damage, and the balance between anti-ROS response and DNA damage play a key role on the cellular responses. The JAK-STAT signal transduction pathway was particularly involved in silver-NP/Gel complex-induced toxic effects. These biological responses eventually decide the fortune of the cells, survival or apoptosis.
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