Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells.
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.
Kim
Soohee
S
College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
Choi
Ji Eun
JE
Choi
Jinhee
J
Chung
Kyu-Hyuck
KH
Park
Kwangsik
K
Yi
Jongheop
J
Ryu
Doug-Young
DY
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
D012834:Silver; D008668:Metallothionein; D012835:Silver Nitrate; D002374:Catalase; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human