Article

Abstract 5464: Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses

Particle and Fibre Toxicology (Impact Factor: 7.11). 01/2014; 11(1):6. DOI: 10.1186/1743-8977-11-6
Source: PubMed

ABSTRACT

Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 mug/cm2 MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 mum optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 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 G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels.

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Available from: Linda M Sargent, Feb 05, 2014
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    • "Chenbo et al.[17][18]studied change in cellular biomechanics with exposer of carbon nanotubes and cytotoxicity effect of MWCNT (Multiwall carbon nanotubes) on human lung epithelial cells. Similarly, Seigrist et al.[19]reported genotoxicity caused by MWCNT. Zhang et al.[20]studied effect of nitrogen doped carbon QDs on living (Hela) cell and as selective probe for Fe. "

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    • "Tumor invasion has been shown to be associated with centrosome disruption and rapidly evolving errors in chromosome number (D'Assoro et al., 2002; Lingle et al., 2002; Pitot, 1993). As MWCNT in vitro have been shown to be bioactive and have effects on centrosome fragmentation, disruption of the cell cycle and errors in chromosome number (Siegrist et al., 2014), these pathways may be reflective of the cytotoxic and aneugenic effects of MWCNT. The top five canonical pathways associated with the MCA+MWCNT group are involved in lipid metabolism and glycolysis; the inflammatory response ; cell proliferation, invasion and tumor immune evasion; and leukocyte migration. "
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