title: Genotoxic and cell-transforming effects of titanium dioxide nanoparticles.
abstract: The in vitro genotoxic and the soft-agar anchorage independent cell transformation ability of titanium dioxide nanoparticles (nano-TiO2) and its microparticulated form has been evaluated in human embryonic kidney (HEK293) and in mouse embryonic fibroblast (NIH/3T3) cells. Nano-TiO2 of two different sizes (21 and 50 nm) were used in this study. The comet assay, with and without the use of FPG enzyme, the micronucleus assay and the soft-agar colony assay were used. For both the comet assay and the frequency of micronuclei a statistically significant induction of DNA damage, was observed at the highest dose tested (1000 µg/mL). No oxidative DNA damage induction was observed when the comet assay was complemented with the use of FPG enzyme. Furthermore, long-term exposure to nano-TiO2 has also proved to induce cell-transformation promoting cell-anchorage independent growth in soft-agar. Results were similar for the two nano-TiO2 sizes. Negative results were obtained when the microparticulated form of TiO2 was tested, indicating the existence of important differences between the microparticulated and nanoparticulated forms. As a conclusion it should be indicated that the observed genotoxic/tranforming effects were only detected at the higher dose tested (1000 µg/mL) what play down the real risk of environmental exposures to this nanomaterial.
authors.affiliation: Akdeniz University, Faculty of Sciences, Department of Biology, 07058 Antalya, Turkey; Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain.
authors.forename: Eşref
authors.initials: E
authors.lastname: Demir
authors.affiliation: Medical Biology Department, School of Medicine, Pamukkale University, Kinikli, Denizli, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Akça
authors.affiliation: Akdeniz University, Faculty of Sciences, Department of Biology, 07058 Antalya, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Turna
authors.affiliation: Akdeniz University, Faculty of Sciences, Department of Biology, 07058 Antalya, Turkey.
authors.forename: Sezgin
authors.initials: S
authors.lastname: Aksakal
authors.affiliation: Antalya Technopark Babylife Cord Blood Bank and Stem Cell Research Center, 07058 Antalya, Turkey.
authors.forename: Durmuş
authors.initials: D
authors.lastname: Burgucu
authors.affiliation: Akdeniz University, Faculty of Sciences, Department of Biology, 07058 Antalya, Turkey.
authors.forename: Bülent
authors.initials: B
authors.lastname: Kaya
authors.affiliation: Medical Biology Department, School of Medicine, Pamukkale University, Kinikli, Denizli, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Tokgün
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Vales
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Spain.
authors.forename: Amadeu
authors.initials: A
authors.lastname: Creus
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Spain. Electronic address: ricard.marcos@uab.es.
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
mesh_terms: D020552:Comet Assay; D057809:HEK293 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*
chemical_list: D009153:Mutagens; C009495:titanium dioxide; D014025:Titanium
keywords: Comet assay; HEK293 and NIH/3T3 cells; Micronucleus assay; Nano-TiO(2); Soft-agar assay