title: From the Cover: An Investigation of the Genotoxicity and Interference of Gold Nanoparticles in Commonly Used In Vitro Mutagenicity and Genotoxicity Assays.
abstract: The suitability of 4 in vitro assays, commonly used for mutagenicity and genotoxicity assessment, was investigated in relation to treatment with 14 nm citrate-stabilized gold nanoparticles (AuNPs). Specifically, the Ames test was conducted without metabolic activation, where no mutagenic effects were observed. High resolution transmission electron microscopy and Cytoviva dark-field image analysis showed that AuNPs did not enter the bacterial cells, thus confirming the unreliability of the Ames test for nanoparticle mutagenicity studies. In addition, the Chinese hamster ovary (CHO) cell line was used for Comet, Chromosome aberration and Micronucleus assays. CHO cells were treated with AuNPs for 20 h at 37 °C. Cytotoxicity was not detected by cell impedance studies even though AuNP uptake was confirmed using Cytoviva image analysis. The DNA damage was statistically significant in treated cells when assessed by the Comet assay. However, minimal and nonstatistically significant chromosomal DNA damage was observed using the chromosome aberration and micronucleus assays. In this study, we showed that false positive results obtained with Comet assay may have been due to the possibility of direct contact between the residual, intracellular AuNPs and DNA during the assay procedure. Therefore, the chromosome aberration and micronucleus assays are better suited to assess the genotoxic effects of nanoparticles due to low probability of such direct contact occurring. Genotoxic effect of 14 and 20 nm citrate-stabilized, as well as, 14 nm PCOOH AuNPs were also investigated using chromosome aberration and micronucleus assays. Based on our acceptance criteria for a positive genotoxic response, none of the AuNPs were found to be genotoxic in either of these assays.
authors.affiliation: Toxicology and Biochemistry Department, National Institute for Occupational Health, Johannesburg 2000, Gauteng, South Africa.
authors.forename: Jiya M
authors.initials: JM
authors.lastname: George
authors.affiliation: Toxicology and Biochemistry Department, National Institute for Occupational Health, Johannesburg 2000, Gauteng, South Africa.|Department of Biotechnology and Food Technology, Tshwane University of Technology, Nelson Mandela Drive, Private Bag X680, Pretoria 0001, South Africa.
authors.forename: Millicent
authors.initials: M
authors.lastname: Magogotya
authors.affiliation: Toxicology and Biochemistry Department, National Institute for Occupational Health, Johannesburg 2000, Gauteng, South Africa.|Haematology and Molecular Medicine, School of Pathology, Medical School, University of the Witwatersrand, Parktown, Johannesburg 2001, Gauteng, South Africa.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Vetten
authors.affiliation: Laboratory for Microscopy and Micro-analysis, University of Pretoria, Hatfield Campus, Pretoria 0002, South Africa.
authors.forename: Antoinette V
authors.initials: AV
authors.lastname: Buys
authors.affiliation: Toxicology and Biochemistry Department, National Institute for Occupational Health, Johannesburg 2000, Gauteng, South Africa.|Haematology and Molecular Medicine, School of Pathology, Medical School, University of the Witwatersrand, Parktown, Johannesburg 2001, Gauteng, South Africa.
authors.forename: Mary
authors.initials: M
authors.lastname: Gulumian
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002869:Chromosome Aberrations / Q000139:chemically induced; D019343:Citric Acid / Q000737:chemistry; D020552:Comet Assay; D003412:Cricetulus; D005189:False Positive Reactions; D006046:Gold / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D015162:Micronucleus Tests; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010316:Particle Size; D011310:Preservatives, Pharmaceutical / Q000737:chemistry; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D013499:Surface Properties
chemical_list: D009153:Mutagens; D011310:Preservatives, Pharmaceutical; D019343:Citric Acid; D006046:Gold
keywords: Ames test; CHO cells; Comet assay; Salmonella typhimurium; chromosome aberration assay; gold nanoparticles; micronucleus assay.