Potential pulmonary effects of engineered carbon nanotubes:in vitrogenotoxic effects

Abstract

The development of novel engineered nano-sized materials is a rapidly emerging technology with many applications in medicine and industry. In vitro and in vivo studies have suggested many deleterious effects of carbon nanotube exposure including granulomatous inflammation, release of cytosolic enzymes, pulmonary fibrosis, reactive oxygen damage, cellular atypia, DNA fragmentation, mutation and errors in chromosome number as well as mitotic spindle disruption. The physical properties of the carbon nanotubes make respiratory exposure to workers likely during the production or use of commercial products. Many of the investigations of the genotoxicity of carbon nanotubes have focused on reactive oxygen mediated DNA damage; however, the long thin tubular-shaped carbon nanotubes have a striking similarity to cellular microtubules. The similarity of carbon nanotubes to microtubules suggests a potential to interact with cellular biomolecules, such as the mitotic spindle, as well as the motor proteins that separate the chromosomes during cell division. Disruption of centrosomes and mitotic spindles would result in monopolar, tripolar, and quadrapolar divisions of chromosomes. The resulting aneuploidy is a key mechanism in the potential carcinogenicity of carbon nanotubes.

Exposure to Carbon Nanotubes Leads to Changes in the Cellular Biomechanics

“…Specifically, our study shows that after 24 h exposure, MWCNTs localize at the cell nucleus, with nanotube localization inducing changes in the nucleus mechanics by increasing its stiffness and overall Young's modulus with more than 36.6% than for control cells (either cells exposed to 1 h acids-washed MWCNTs for 1 h or to the control cells). Combining our data with previous reports that indicate that MWCNTs interact with microtubules, [22,46] the mitotic spindle, [22] DNA and cell division apparatus, [17,18] we propose now that the observed stiffness due to exposure to 1 h acids-washed MWCNTs could lead the reorganization of the three-dimensional cellular cytoskeletal network. Such reorganization could potentially disrupt the mitotic spindle, [22] inducing errors in chromosome numbers to be propagated through further cellular division [19] as characteristics of cancer cells.…”

“…[18,19] For instance, our recent studies have shown that 24 to 72 h exposure of epithelial cells to SWCNTs induced centrosome fragmentation and aneuploidy [18,20] similar to the genotoxin vanadium pentoxide. [21] Likewise, cellular exposure to MWCNT disrupted the mitotic spindle by association with microtubules, [22] induced polyploidy [17] and changes in chromosome number in a fashion similar to crocidolite asbestos. [20,23,24] CNTs genotoxicity has been attributed to a variety of factors including metal impurities, length, size, number of walls, surface area, dispersion, and/or CNTs surface functionalization.…”

“…Further, given their applications in the biomedical field, [13,14] understanding how biological systems interact with this nanomaterial is urgently needed to create safer therapies, [14,15] and to regulate occupational exposures. [16,17] Recent work has shown that in vitro and in vivo exposure to SWCNTs can lead to alterations in DNA structure. [18,19] For instance, our recent studies have shown that 24 to 72 h exposure of epithelial cells to SWCNTs induced centrosome fragmentation and aneuploidy [18,20] similar to the genotoxin vanadium pentoxide.…”

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

“…39 However, CNFs generate significant radicals and are more genotoxic than SWCNTs. 43 Sargent et al 44 reported that SWCNTs disrupt centrosomes in dividing lung epithelial cells resulting in multipolar mitosis and aneuploidy. MWCNTs have also been shown to interact with centrosomes preventing normal migration to mitotic poles and resulting in monopolar mitosis.…”

“…Such low doses also reveal CNT-induced cell transformation and aneuploidy instead of cell death. 44,49 …”