RRC ID 37672
Author Kawata K, Osawa M, Okabe S.
Title In vitro toxicity of silver nanoparticles at noncytotoxic doses to HepG2 human hepatoma cells.
Journal Environ Sci Technol
Abstract Although it has been reported that silver nanoparticles (Ag-NPs) have strong acute toxic effects to various cultured cells, the toxic effects at noncytotoxic doses are still unknown. We, therefore, evaluated in vitro toxicity of Ag-NPs at noncytotoxic doses in human hepatoma cell line, HepG2, based on cell viability assay, micronucleus test, and DNA microarray analysis. We also used polystyrene nanoparticles (PS-NPs) and silver carbonate (Ag2CO3) as test materials to compare the toxic effects 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), which 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 induced abnormal cellular morphology, displaying cellular shrinkage and acquisition of an irregular shape. In addition, only Ag-NPs exposure increased the frequency of micronucleus formation up to 47.9 +/- 3.2% of binucleated cells, suggesting that Ag-NPs appear to cause much stronger damages to chromosome than PS-NPs and ionic Ag+. Cysteine, a strong ionic Ag+ ligand, 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.
Volume 43(15)
Pages 6046-51
Published 2009-8-1
DOI 10.1021/es900754q
PMID 19731716
MeSH Cell Line, Tumor Cysteine / chemistry DNA Damage Drug Screening Assays, Antitumor / methods* Gene Expression Profiling Gene Expression Regulation, Neoplastic / drug effects* Humans Ions Metal Nanoparticles / chemistry* Metal Nanoparticles / toxicity* Micronucleus Tests / methods Nanotechnology / methods Oligonucleotide Array Sequence Analysis Oxidative Stress Reactive Oxygen Species Silver / chemistry* Silver / toxicity*
IF 7.149
Times Cited 452
Human and Animal Cells