In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes

Tidsskriftartikel - 2016


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 microg/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/m3) for 4 days, 4 h/day. No systemic genotoxic effects, assessed by the gamma-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 microg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m3). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 microg/cm2), while MWCNT-T increased strand breakage only at 200 microg/cm2. 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


Catalan J, Siivola K, Nymark P, Lindberg H, Suhonen S, Jarventaus H, Koivisto AJ, Moreno C, Vanhala E, Wolff H, Kling K, Jensen KA, Savolainen K, Norppa H. In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes. Nanotoxicology 2016;10(6):794-806.
doi: 10.3109/17435390.2015.1132345

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