title: Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells.
abstract: Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells. Toxicity induced by silver (Ag(+)) ions was studied in parallel using AgNO(3) as the Ag(+) ion source. Using cation exchange treatment, we confirmed that the AgNP solution contained a negligible amount of free Ag(+) ions. Metal-responsive metallothionein 1b (MT1b) mRNA expression was not induced in AgNP-treated cells, while it was induced in AgNO(3)-treated cells. These results indicate that AgNP-treated cells have limited exposure to Ag(+) ions, despite the potential release of Ag(+) ions from AgNPs in cell culture. AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and induced intracellular oxidative stress. AgNPs exhibited cytotoxicity with a potency comparable to that of Ag(+) ions in in vitro cytotoxicity assays. However, the toxicity of AgNPs was prevented by use of the antioxidant N-acetylcysteine, and AgNP-induced DNA damage was also prevented by N-acetylcysteine. AgNO(3) treatment induced oxidative stress-related glutathione peroxidase 1 (GPx1) and catalase expression to a greater extent than AgNP exposure, but treatment with AgNO(3) and AgNPs induced comparable superoxide dismutase 1 (SOD1) expression levels. Our findings suggest that AgNP cytotoxicity is primarily the result of oxidative stress and is independent of the toxicity of Ag(+) ions.
authors.affiliation: College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Soohee
authors.initials: S
authors.lastname: Kim
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
authors.forename: Kyu-Hyuck
authors.initials: KH
authors.lastname: Chung
authors.forename: Kwangsik
authors.initials: K
authors.lastname: Park
authors.forename: Jongheop
authors.initials: J
authors.lastname: Yi
authors.forename: Doug-Young
authors.initials: DY
authors.lastname: Ryu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002374:Catalase / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D008668:Metallothionein / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012834:Silver / Q000633:toxicity*; D012835:Silver Nitrate / Q000633:toxicity; D000094765:Glutathione Peroxidase GPX1
chemical_list: D012834:Silver; D008668:Metallothionein; D012835:Silver Nitrate; D002374:Catalase; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human