title: Cytotoxicity and genotoxicity assessment of silver nanoparticles in mouse.
abstract: Silver nanoparticles (AgNPs) are among the most commercially used nanomaterials and their toxicity and genotoxicity are controversial. Although many in vitro studies have been conducted to evaluate the genotoxicity of AgNPs, in vivo genotoxicity studies on the nanomaterials are limited. Given the unique physicochemical properties and complex pharmacokinetics behavior of nanoparticles (NPs), in vivo genotoxicity assessment of AgNPs is badly needed. In this study, the clastogenicity and mutagenicity of AgNPs with different sizes and coatings were evaluated using mouse micronucleus (MN) assay, Pig-a assay and Comet assay. Five 7-week-old male B6C3F1 mice per group were treated with 5 nm polyvinylpyrrolidone (PVP)-coated AgNPs at a single dose of 0.5, 1.0, 2.5, 5.0, 10.0 or 20.0 mg/kg body weight (bw) via intravenous injection for both the MN and Pig-a assays; or with 15-100 nm PVP- or 10-80 nm silicon-coated AgNPs at a single or 3-day repeated dose of 25.0 mg/kg bw for the MN assay and Comet assay in mouse liver. Inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM) analyses indicated that AgNPs reached the testing tissues (bone marrow for the MN and Pig-a assays and liver for the Comet assay). Although there was a reduction of reticulocytes in the PVP-coated AgNPs-treated animals, indicating cytotoxicity of the AgNPs, none of the treatments resulted in a significant increase of either mutant frequencies in the Pig-a gene or the percent of micronucleated reticulocyte over the concurrent controls. However, both the PVP- and silicon-coated AgNPs induced oxidative DNA damage in mouse liver. These results demonstrate that the AgNPs can reach mouse bone marrow and liver, and generate cytotoxicity to the reticulocytes and oxidative DNA damage to the liver.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA .
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Javed A
authors.initials: JA
authors.lastname: Bhalli
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Mason G
authors.initials: MG
authors.lastname: Pearce
authors.forename: Rakhshinda
authors.initials: R
authors.lastname: Sadiq
authors.forename: Candice K
authors.initials: CK
authors.lastname: Cunningham
authors.forename: M Yvonne
authors.initials: MY
authors.lastname: Jones
authors.forename: William A
authors.initials: WA
authors.lastname: Monroe
authors.forename: Paul C
authors.initials: PC
authors.lastname: Howard
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009152:Mutagenicity Tests; D012834:Silver / Q000737:chemistry*
chemical_list: D012834:Silver
keywords: Clastogenicity; in vivo comet assay; in vivo micronucleus assay; in vivo pig-a gene mutation assay; mutagenicity; silver nanoparticles