title: Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays.
abstract: The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.
authors.affiliation: a Division of Genetic and Molecular Toxicology .
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: a Division of Genetic and Molecular Toxicology .
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Division of Genetic and Molecular Toxicology .
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: b Nanotechnology Core Facility , and.
authors.forename: Taylor
authors.initials: T
authors.lastname: Ingle
authors.affiliation: b Nanotechnology Core Facility , and.
authors.forename: Margie Yvonne
authors.initials: MY
authors.lastname: Jones
authors.affiliation: a Division of Genetic and Molecular Toxicology .
authors.forename: Nan
authors.initials: N
authors.lastname: Mei
authors.affiliation: c Division of Biochemical Toxicology , National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson , AR , USA .
authors.forename: Mary D
authors.initials: MD
authors.lastname: Boudreau
authors.affiliation: b Nanotechnology Core Facility , and.
authors.forename: Candice K
authors.initials: CK
authors.lastname: Cunningham
authors.affiliation: a Division of Genetic and Molecular Toxicology .|d Institute of Molecular Biology and Biotechnology, The University of Lahore , Pakistan , and.
authors.forename: Mazhar
authors.initials: M
authors.lastname: Abbas
authors.affiliation: b Nanotechnology Core Facility , and.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Paredes
authors.affiliation: e Center for Veterinary Medicine, U.S. Food and Drug Administration , Rockville , MD , USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: a Division of Genetic and Molecular Toxicology .
authors.forename: Martha M
authors.initials: MM
authors.lastname: Moore
authors.affiliation: b Nanotechnology Core Facility , and.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Howard
authors.affiliation: a Division of Genetic and Molecular Toxicology .
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D012835:Silver Nitrate / Q000737:chemistry / Q000633:toxicity; D013499:Surface Properties
chemical_list: D009153:Mutagens; D012834:Silver; D012835:Silver Nitrate
keywords: Ames test; genotoxicity; in vitro micronucleus assay; mouse lymphoma assay; silver nanoparticles