Induction of aneuploidy by single walled carbon nanotubes.
Sargent-LM; Shvedova-AA; Hubbs-AF; Lowry-DT; Kashon-ML; Murray-A; Kisin-E; Benkovic-SA; Miller-DB; McKinstry-KT; Reynolds-SH
Toxicologist 2009 Mar; 108(1):411
Engineered carbon nanoparticles are newly emerging manufactured particles with potential applications in multiple fields, including electronics, computers, and aerospace. The low density and small size of these persistent particles makes respiratory exposures to workers likely during the production or use of various commercial products. To examine the potential of nanotubes to induce genetic damage in normal lung cells, primary and immortalized human small airway epithelial cells were cultured and then exposed to single walled carbon nanotubes (SWCNTs) or a positive control vanadium pentoxide. The nanotubes had an average diameter of 1.1 nanometer and a length of 50-100 microns. Cellular tubulin, mitotic spindle integrity and centriole number were determined by immunofluorescence for betatubulin and centrin and photographed using fluorescent and confocal laser scanning microscopy. The chromosome number was examined by fluorescent in situ hybridization. After 24 hours of exposure to either SWCNT or vanadium pentoxide, binucleate cells, bundled tubulin and fragmented centrosomes were present. Abnormalities included changes in mitotic spindles, including multiple poles that resulted in aneuploid chromosome number. Confocal microscopy demonstrated nanotubes within the nucleus that were in association with cellular and mitotic tubulin as well as the chromatin. These findings indicate that these SWCNTs can enter the nucleus, inducing mitotic spindle disruption and abnormal chromosome number. Thus, our study indicates that direct interaction between chromatin and SWCNTs may contribute to genetic changes in somatic cells. Exposure to agents that interfere with the formation and movement of the mitotic spindle apparatus and cause abnormalities in chromosome number result in a greater risk of cancer.
Biological-effects; Biological-factors; Cancer; Cancer-rates; Cellular-reactions; Cell-biology; Cell-damage; Cytology; Exposure-assessment; Exposure-levels; Exposure-methods; Fibrous-bodies; Fibrous-dusts; Genetic-disorders; Irritants; Inhalation-studies; Lung-cells; Lung-disorders; Lung-irritants; Microscopic-analysis; Microscopy; Particle-aerodynamics; Particulate-dust; Particulates; Respiratory-irritants; Respiratory-system-disorders; Risk-factors; Statistical-analysis; Workplace-studies; Work-environment; Nanotechnology
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland