title: Global gene expression profiling of human lung epithelial cells after exposure to nanosilver.
abstract: 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.
authors: Department of Public Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Rasmus
authors: R
authors: Foldbjerg
authors: Eveline S
authors: ES
authors: Irving
authors: Yuya
authors: Y
authors: Hayashi
authors: Duncan S
authors: DS
authors: Sutherland
authors: Kasper
authors: K
authors: Thorsen
authors: Herman
authors: H
authors: Autrup
authors: Christiane
authors: C
authors: Beer
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009336:Necrosis / Q000139:chemically induced; D020411:Oligonucleotide Array Sequence Analysis; D010316:Particle Size; D025341:Principal Component Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012835:Silver Nitrate / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D012835:Silver Nitrate