title: Genotoxicity of titanium dioxide nanoparticles.
abstract: Titanium dioxide nanoparticles (TiO(2)-NPs, <100 nm) are increasingly being used in pharmaceuticals and cosmetics due to the unique properties derived from their small sizes. However, their large surface-area to mass ratio and high redox potential may negatively impact human health and the environment. TiO(2)-NPs can cause inflammation, pulmonary damage, fibrosis, and lung tumors and they are possibly carcinogenic to humans. Because cancer is a disease involving mutation, there are a large number of studies on the genotoxicity of TiO(2)-NPs. In this article, we review the results that have been reported in the literature, with a focus on data generated from the standard genotoxicity assays. The data include genotoxicity results from the Ames test, in vitro and in vivo Comet assay, in vitro and in vivo micronucleus assay, sister chromatid exchange assay, mammalian cell hypoxanthine-guanine phosphoribosyl transferase gene assay, the wing somatic mutation and recombination assay, and the mouse phosphatidylinositol glycan, class A gene assay. Inconsistent results have been found in these assays, with both positive and negative responses being reported. The in vitro systems for assessing the genotoxicity of TiO(2)-NPs have generated a greater number of positive results than the in vivo systems, and tests for DNA and chromosome damage have produced more positive results than the assays measuring gene mutation. Nearly all tests for measuring the mutagenicity of TiO(2)-NPs were negative. The current data indicate that the genotoxicity of TiO(2)-NPs is mediated mainly through the generation of oxidative stress in cells.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA. Electronic address: tao.chen@fda.hhs.gov.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D004249:DNA Damage; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D009152:Mutagenicity Tests; D014025:Titanium / Q000737:chemistry
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: Ames test; Carcinogenicity; Class A gene; Comet; Genotoxicity; Hypoxanthine-guanine phosphoribosyl transferase gene; Micronucleus; Phosphatidylinositol glycan; Sister chromatid exchange; Titanium dioxide nanoparticles; Wing point mutation