In Vitro Toxicity of Silver Nanoparticles at Noncytotoxic Doses to HepG2 Human Hepatoma Cells

Although it has been reported that silver nanoparticles (Ag-NPs) have strong acute toxic effects to various cultured the toxic effects at noncytotoxic doses are still unknown. We, therefore, evaluated in vitro toxicity of doses in human hepatoma cell line, HepG2, based on cell viability assay, micronucleus test, and DNA microarray We also used polystyrene nanoparticles (PS-NPs) and silver carbonate (Ag2CO3) as test materials to compare the toxic with respect to different raw chemical composition and form of silver. The cell viability assay demonstrated that Ag-NPs accelerated cell proliferation at low doses (<0.5 mg/L), was supported by the DNA microarray analysis showing significant induction of genes associated with cell cycle progression. However, only Ag-NPs exposure exhibited a significant cytotoxicity at higher doses (> 1.0 mg/L) and abnormal cellular morphology, displaying cellular shrinkage and acquisition of an irregular shape. In addition, only exposure increased the frequency of micronucleus formation up to 47.9 +/- 3.2% of binucleated cells, suggesting that appear to cause much stronger damages to chromosome than PS-NPs and ionic Ag+. Cysteine, a strong ionic Ag+ only partially abolished the formation of micronuclei mediated by Ag-NPs and changed the gene expression, indicating that ionic Ag+ derived from Ag-NPs could not fully explain these biological actions, Based on these discussions, it is concluded that both "nanosized particle of Ag" as well as "ionic Ag+" contribute to the toxic effects of Ag-NPs.