Toxicity of Silver Nanoparticles as Assessed by Global Gene Expression Analysis

Silver nanoparticles (Ag-NPs) showed a toxic effect on He La cells. For cells exposed to Ag-NPs at a concentration of 20 mu g/ml for 24 h and 48 h, the number of viable cells decreased by 45.4 +/- 7.3% and 47.3 +/- 8.8%, respectively. Cells exposed to Ag-NPs for 24 h up- and down-regulated 2065 and 1286 genes, respectively. In a Gene Ontology (GO) analysis, the genes up-regulated by Ag-NPs were classified into functional categories that included various primary metabolic processes, cellular processes, and stress responses. Most of these functional changes, as represented by up-regulated gene expression, could be attributed to Ag ions released from Ag-NPs. In addition, functional categories identified by the categorization of up-regulated genes suggest that the reduction in the viable cell number after exposure to Ag-NPs could be attributed to apoptosis but not cell cycle arrest. Most genes down-regulated by Ag-NPs could also be attributed to exposure to released Ag ions, but most of the functional changes caused by genes down-regulated by Ag-NPs could be attributed to Ag-NPs themselves but not to released Ag ions. For cells exposed to Ag-NPs for 48 h, the number of genes with altered expression was significantly decreased relative to that of cells exposed for 24 h, suggesting that cells may be able to cope with the toxicity of Ag-NPs within 48 h.