title: Long-term exposures to low doses of titanium dioxide nanoparticles induce cell transformation, but not genotoxic damage in BEAS-2B cells.
abstract: There is a great interest in a better knowledge of the health effects caused by nanomaterials exposures and, in particular to those induced by titanium dioxide nanoparticles (nano-TiO2) due to its high use and increasing presence in the environment. To add new information on its potential genotoxic/carcinogenic risk, we have carried out experiments using chronic exposures (up to 4 weeks), low doses, and the BEAS-2B cell line that, as a human bronchial epithelium cells, can be considered a good cell target. Cell uptake has been assessed by transmission electron microscopy (TEM) and flow cytometry (FC); genotoxicity was evaluated using the comet and the micronucleus (MN) assays; and cell-transforming ability was evaluated using the soft-agar assay to detect anchorage-independent cell growth. Results show an important cell uptake at all the tested doses and sampling times used (except for 1 µg/mL and 24-h exposure). Nevertheless, no genotoxic effects were observed in the comet and in the MN assays. This lack of genotoxic effect agrees with the FC results showing no induction of intracellular reactive oxygen species (ROS), the data from the comet assay with formamidopyrimidine DNA glycosylase (FPG) enzyme showing no induction of oxidized bases, and the lack of induction of expression of heme-oxygenase (HO-1) gene both at the RNA and protein level. On the contrary, significant increases in the number of clones growing in an anchorage-independent way were observed. This study would indicate a potential carcinogenic risk associated to nano-TiO2 exposure, not mediated by a genotoxic mechanism.
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona , Bellaterra , Spain , and.
authors.forename: Gerard
authors.initials: G
authors.lastname: Vales
authors.forename: Laura
authors.initials: L
authors.lastname: Rubio
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
mesh_terms: D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D020552:Comet Assay; D016207:Cytokines / Q000235:genetics; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000706:statistics & numerical data; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
keywords: Cell transformation; Titanium dioxide; chronic exposure; comet; micronucleus