Global gene expression profiling of human lung epithelial cells after exposure to nanosilver

The toxic effects of silver nanoparticles (AgNPs) on cells are well established, but only limited studies on the effect of AgNPs and silver ions on the cellular transcriptome have been performed. In this study, the effect of AgNPs on the gene expression in the human lung epithelial cell line A549 ex...

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Published in:Toxicological sciences 2012-11, Vol.130 (1), p.145-157
Main Authors: Foldbjerg, Rasmus, Irving, Eveline S, Hayashi, Yuya, Sutherland, Duncan S, Thorsen, Kasper, Autrup, Herman, Beer, Christiane
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Cell Cycle - drug effects
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Gene Expression Profiling
Gene Expression Regulation - drug effects
Genome-Wide Association Study
Humans
Lung Neoplasms
Metal Nanoparticles - toxicity
Metal Nanoparticles - ultrastructure
Necrosis - chemically induced
Oligonucleotide Array Sequence Analysis
Particle Size
Principal Component Analysis
Reactive Oxygen Species - metabolism
Respiratory Mucosa - drug effects
Respiratory Mucosa - metabolism
Respiratory Mucosa - pathology
Silver Nitrate - toxicity
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Summary:The toxic effects of silver nanoparticles (AgNPs) on cells are well established, but only limited studies on the effect of AgNPs and silver ions on the cellular transcriptome have been performed. In this study, the effect of AgNPs on the gene expression in the human lung epithelial cell line A549 exposed to 12.1 µg/ml AgNPs (EC20) for 24 and 48h was compared with the response to control and silver ion (Ag(+)) treated cells (1.3 µg/ml) using microarray analysis. Twenty-four hours to AgNP altered the regulation of more than 1000 genes (more than twofold regulation), whereas considerably fewer genes responded to Ag(+) (133 genes). The upregulated genes included members of the metallothionein, heat shock protein, and histone families. As expected from the induction of meta l lothionein and heat shock protein genes, Ag(+) and AgNP treatment resulted in intracellular production of reactive oxygen species but did not induce apoptosis or necrosis at the concentrations used in this study. In addition, the exposure to AgNPs influenced the cell cycle and led to an arrest in the G2/M phase as shown by cell cycle studies by flow cytometry and microscopy. In conclusion, although the transcriptional response to Ag(+) exposure was highly related to the response caused by AgNPs, our findings suggest that AgNPs, due to their particulate form, affect exposed cells in a more complex way.
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfs225