Induction of mitotic spindle aberrations by occupationally relevant doses of single-walled carbon nanotubes.
Sargent-L; Hubbs-AF; Shvedova-AA; Kashon-ML; Salisbury-JL; Lowry-DT; Murray-A; Kisin-E; Benkovic-SA; McKinstry-KT; Reynolds-SH
Toxicologist 2010 Mar; 114(1):170
Engineered carbon nanotubes are newly emerging manufactured particles with potential applications in electronics, computers, aerospace and medicine. The low density and small size of these biologically persistent particles makes respiratory exposures to workers likely during the production or use of commercial products.We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 96, 48 and 24 micrograms/centimeter squared single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 hours.We have now demonstrated fragmented centrosomes, multiple mitotic spindle poles and aneuploid chromosome number at doses equivalent to the permissible exposure limit. The nanotube bundles are similar to the size of microtubules that form the mitotic spindle and may be incorporated into the mitotic spindle apparatus. Confocal microscopy demonstrated nanotubes within the nucleus and in association with mitotic tubulin, the centrosomes and the chromatin in cells exposed to 2.4, 0.24 and 0.024 micrograms/centimeter squared SWCNT. The lower doses do not cause toxicity by Alamar Blue assay, apoptosis by TUNEL or reduction in colony formation after 24 hours. However, after 3 days, the colony formation of the primary cells was reduced. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. Centrosome fragmentation, mitotic spindle disruption and aneuploidy are characteristics of cancer cells and may lead to an increased risk of cancer. *The authors contributed equally to the work.
Biological-effects; Biological-monitoring; Cell-biology; Cellular-reactions; Exposure-assessment; Exposure-levels; Exposure-methods; Microscopic-analysis; Nanotechnology; Particulates; Pulmonary-system; Respiratory-hypersensitivity; Respiratory-irritants
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah