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Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube (SWCNT)-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
Single-walled carbon nanotube-induced mitotic disruption
L M Sargent1, A F Hubbs, S-H Young
1National Institute for Occupational Safety and Health, Morgantown, WV 26505, United States. lqs1@cdc.gov
Single-walled carbon nanotubes (SWCNTs) disrupt cell division and damage DNA at occupationally relevant doses. This can lead to increased cell proliferation, potentially increasing cancer risk, highlighting the need for safe handling of SWCNTs.
Area of Science:
- Nanotechnology
- Cell Biology
- Occupational Health
Background:
- Carbon nanotubes (CNTs) are widely used in various industries.
- Occupational exposure to CNTs poses risks due to their small size and persistence.
- Previous studies indicated mitotic spindle aberrations from CNT exposure.
Purpose of the Study:
- To investigate the effects of single-walled carbon nanotubes (SWCNTs) on human airway epithelial cells at occupationally relevant concentrations.
- To assess cellular damage, including mitotic spindle disruption and genotoxicity, following SWCNT exposure.
Main Methods:
- Primary and immortalized human airway epithelial cells were exposed to SWCNTs for 24-72 hours.
- Doses were equivalent to 20 weeks of exposure at the Permissible Exposure Limit.
- Cellular damage, including centrosome fragmentation, mitotic spindle disruption, aneuploidy, and cytotoxicity, was analyzed.
- Nanotube localization within cells was examined using 3D reconstructions.
Main Results:
- SWCNT exposure at occupationally relevant doses caused fragmented centrosomes, disrupted mitotic spindles, and aneuploidy.
- Multipolar mitotic spindles constituted 95% of disrupted mitoses, indicating a mitotic checkpoint response.
- SWCNTs were found within centrosome structures and associated with spindle microtubules.
- Significant cytotoxicity was observed after three days, but increased proliferation occurred seven days post-exposure.
Conclusions:
- SWCNTs disrupt the mitotic spindle and centrosome integrity at occupationally relevant doses.
- Observed aneuploidy and increased proliferation suggest a potential role in tumorigenesis and cancer progression.
- Caution is advised during the handling and processing of SWCNTs due to their genotoxic potential.
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