Genotoxicity of multiwalled carbon nanotubes.
Reynolds-SH; Dinu-C; Lowry-DT; Kashon-ML; Hubbs-AF; Stanley-B; Salisbury-JL; Mastovich-J; Kristin-B; Sturgeon-J; Keane-M; Lorenzo-C; Sargent-L
Toxicologist 2013 Mar; 132(1):92
Carbon nanotubes have many unique applications in industry and medicine. Although the low density and small size of carbon nanotubes makes respiratory exposures to workers likely during the production or use of commercial products, the genotoxicity is not fully investigated. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In order to investigate whether mitotic spindle damage was unique to SWCNT, we examined mitotic spindle aberrations following dosing of cells to multi-walled carbon nanotubes (MWCNT) at concentrations anticipated in the workplace. MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number. The data further showed that monopolar mitotic spindles comprised 95% of the disrupted mitoses. Cell cycle analysis demonstrated a greater number of cells in G1 and S-phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and the G2 block in the cell cycle observed in SWCNT-induced disruption. Three dimensional reconstructions showed carbon nanotubes integrated with the microtubules, the DNA and within the centrosome structure. The lower doses did not cause cytotoxicity or apoptosis 24 hours after exposure; however, after 72 hours, significant cytotoxicity was observed in the MWCNT-exposed cells. One month following exposure, MWCNT-treated cells had a dramatic increase in both size and number of colonies. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant doses.
Toxicology; Nanotechnology; Cell-alteration; Cellular-reactions; Cell-damage; Exposure-assessment; Dose-response; Genotoxic-effects; Genotoxicity; Chromosome-damage; Chromosome-disorders; Mitosis; Cellular-reactions; Cytology; Cytotoxicity; DNA-damage
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas