title: Toxicological evaluation of representative silver nanoparticles in macrophages and epithelial cells.
abstract: Silver nanoparticles (Ag-NPs) are highly relevant for human and environmental exposure due to their widespread use in consumer and medical products and various applications. Thus, there is a need for evaluating potential toxicity of these NPs. The objective of this study was to investigate the toxic effects of the OECD (Organization for Economic Co-operation and Development) representative Ag-NPs, NM300K, in mouse macrophage J774A.1 and human colonic epithelial HT29 cells, using multiple endpoint assays. Exposure of test cells to different concentrations (1-250 μg/mL; total silver content) of NM300K for 24h showed a dose-dependent decrease in cell viability. At high doses, NM300K altered cell shape and induced the formation of vacuolar structures, as examined by confocal and electron microscopy. Moreover, NM300K induced inflammation as evidenced by the elevated levels of pro-inflammatory cytokines. Finally, high doses of NM300K led to increased production of reactive oxygen species and induction of oxidative stress, leading to oxidative DNA damage and apoptosis in test cells. At equivalent silver concentrations, NM300K were less cytotoxic than AgNO3. However, the similar patterns in the effects of NM300K and AgNO3 throughout the assessed toxicological endpoints suggest that Ag(+) released from these NPs by dissolution could be a primary contributor to toxicity. This study is among the first to characterize the potential toxicity of OECD representative AgNPs in vitro, and provides additional insight into the biological mechanisms associated with Ag-NP toxicity.
authors.affiliation: Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, HECSB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Kathy C
authors.initials: KC
authors.lastname: Nguyen
authors.affiliation: Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, HECSB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Richards
authors.affiliation: University of Ottawa, Department of Biology and Centre for Advanced Research in Environmental Genomics, Ottawa, Ontario, Canada.
authors.forename: Andrey
authors.initials: A
authors.lastname: Massarsky
authors.affiliation: University of Ottawa, Department of Biology and Centre for Advanced Research in Environmental Genomics, Ottawa, Ontario, Canada.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Moon
authors.affiliation: Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, HECSB, Health Canada, Ottawa, Ontario, Canada. Electronic address: Azam.Tayabali@hc-sc.gc.ca.
authors.forename: Azam F
authors.initials: AF
authors.lastname: Tayabali
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D012834:Silver; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione
keywords: Apoptosis; DNA damage; Epithelial; Macrophage; NM300K; Oxidative stress; Silver nanoparticles; Toxicity