title: Role of the crystalline form of titanium dioxide nanoparticles: Rutile, and not anatase, induces toxic effects in Balb/3T3 mouse fibroblasts.
abstract: The wide use of titanium dioxide nanoparticles (TiO2 NPs) in industrial applications requires the investigation of their effects on human health. In this context, we investigated the effects of nanosized and bulk titania in two different crystalline forms (anatase and rutile) in vitro. By colony forming efficiency assay, a dose-dependent reduction of the clonogenic activity of Balb/3T3 mouse fibroblasts was detected in the presence of rutile, but not in the case of anatase NPs. Similarly, the cell transformation assay and the micronucleus test showed that rutile TiO2 NPs were able to induce type-III foci formation in Balb/3T3 cells and appeared to be slightly genotoxic, whereas anatase TiO2 NPs did not induce any significant neoplastic or genotoxic effect. Additionally, we investigated the interaction of TiO2 NPs with Balb/3T3 cells and quantified the in vitro uptake of titania using mass spectrometry. Results showed that the internalization was independent of the crystalline form of TiO2 NPs but size-dependent, as nano-titania were taken up more than their respective bulk materials. In conclusion, we demonstrated that the cytotoxic, neoplastic and genotoxic effects triggered in Balb/3T3 cells by TiO2 NPs depend on the crystalline form of the nanomaterial, whereas the internalization is regulated by the particle size.
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, VA, Italy. Electronic address: chiara.uboldi@imbe.fr.
authors.forename: Chiara
authors.initials: C
authors.lastname: Uboldi
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, VA, Italy. Electronic address: patricia.urban-lopez@ec.europa.eu.
authors.forename: Patricia
authors.initials: P
authors.lastname: Urbán
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, VA, Italy. Electronic address: douglas.gilliland@ec.europa.eu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gilliland
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, VA, Italy. Electronic address: eda_adenov@yahoo.com.
authors.forename: Edyta
authors.initials: E
authors.lastname: Bajak
authors.affiliation: Natural History Museum, Department of Earth Sciences, London SW7 5BD, UK; University of Birmingham, School of Geography, Earth and Environmental Sciences, Birmingham B15 2TT, UK. Electronic address: e.valsamijones@bham.ac.uk.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Valsami-Jones
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, VA, Italy. Electronic address: jessica.ponti@ec.europa.eu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponti
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, VA, Italy. Electronic address: francois.rossi@ec.europa.eu.
authors.forename: François
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D015162:Micronucleus Tests; D046529:Microscopy, Electron, Transmission; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D009153:Mutagens; C009495:titanium dioxide; D014025:Titanium
keywords: Cytotoxicity; Genotoxicity; Micronucleus; Morphological neoplastic transformation; Titanium dioxide nanoparticles; Uptake