title: In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes.
abstract: Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) in vitro (primary genotoxicity) and in vivo (primary or secondary genotoxicity). C57Bl/6 mice showed a dose-dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24 h after a single pharyngeal aspiration of MWCNT-S (1-200 μg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2-10.8 mg/m(3)) for 4 d, 4 h/d. No systemic genotoxic effects, assessed by the γ-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related decrease in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1-200 μg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m(3)). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 μg/cm(2)), while MWCNT-T increased strand breakage only at 200 μg/cm(2). Neither of the MWCNTs was able to induce micronuclei in vitro. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs.
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .|b Department of Anatomy , Embryology and Genetics, University of Zaragoza , Zaragoza , Spain .
authors.forename: Julia
authors.initials: J
authors.lastname: Catalán
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Kirsi M
authors.initials: KM
authors.lastname: Siivola
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .|c Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden , and.
authors.forename: Penny
authors.initials: P
authors.lastname: Nymark
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Hanna
authors.initials: H
authors.lastname: Lindberg
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Satu
authors.initials: S
authors.lastname: Suhonen
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Hilkka
authors.initials: H
authors.lastname: Järventaus
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .|d Danish Centre for Nanosafety, National Research Centre for the Working Environment , Copenhagen , Denmark.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Koivisto
authors.affiliation: b Department of Anatomy , Embryology and Genetics, University of Zaragoza , Zaragoza , Spain .
authors.forename: Carlos
authors.initials: C
authors.lastname: Moreno
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Esa
authors.initials: E
authors.lastname: Vanhala
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.affiliation: d Danish Centre for Nanosafety, National Research Centre for the Working Environment , Copenhagen , Denmark.
authors.forename: Kirsten I
authors.initials: KI
authors.lastname: Kling
authors.affiliation: d Danish Centre for Nanosafety, National Research Centre for the Working Environment , Copenhagen , Denmark.
authors.forename: Keld Alstrup
authors.initials: KA
authors.lastname: Jensen
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Kai
authors.initials: K
authors.lastname: Savolainen
authors.affiliation: a Nanosafety Research Centre, Finnish Institute of Occupational Health , Helsinki , Finland .
authors.forename: Hannu
authors.initials: H
authors.lastname: Norppa
mesh_terms: D000818:Animals; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D037742:Nanotubes, Carbon / Q000633:toxicity*
chemical_list: D037742:Nanotubes, Carbon
keywords: Comet assay; DNA damage; genotoxicity; micronuclei; multi-walled carbon nanotubes