Mechanism of induction of binucleated cells by multiwalled carbon nanotubes as revealed by live-cell imaging analysis

Our plain-English summary of Mechanism of induction of binucleated cells by multiwalled carbon nanotubes as revealed by live-cell imaging analysis, by M. Yasui, N. Kamoshita, T. Nishimura, et al (Genes and Environment, 2015).

The study

• Authors: M. Yasui, N. Kamoshita, T. Nishimura, M. Honma
• Journal: Genes and Environment
• Published: 2015;37:6
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Asbestos-induced formation of mesothelioma has been attributed to phenotypic and morphological changes in cells caused by polyploidization and aneuploidization, and multiwalled carbon nanotubes (MWCNTs) are suspected to have similar adverse effects due to the similarity in their physical form. MWCNTs and crocidolite, a kind of asbestos, show similar genotoxicity characteristics in vitro, including induction of binucleated cells. We here focused on the mechanisms underlying polyploidization during cell division on exposure to MWCNTs and conducted confocal live-cell imaging analysis using MDA-435 human breast cancer cells in which chromosomes and centromeres were visualized using fluorescent proteins.

Findings: During anaphase, relatively short MWCNT fibers (approximately 5 μm) migrated rapidly to either of the daughter cells, whereas some long MWCNT fibers (approximately 20 μm) remained inside the contractile ring and induced the formation of binucleated cells through impairment of cytokinesis. This toxicity mechanism has also been observed with crocidolite.

Conclusions: Our findings indicate that the mechanism of polyploidization by MWCNTs is very similar to that observed with crocidolite.

In plain English

This short report described a laboratory study of cells, not people. The authors filmed dividing human breast cancer cells (the MDA-435 line, with fluorescently labeled chromosomes) exposed to multiwalled carbon nanotubes (MWCNT-7) at 0, 12.7, 25.3 or 50.6 μg/mL. Among untreated cells, 93 of 232 completed division and 4 died during division. At the three rising doses, 40 of 112, 49 of 170 and 34 of 282 cells completed division, and 4, 11 and 21 died. Of those same cells, 0, 5 and 1 ended up with two nuclei. The article's printed percentages do not all equal count divided by total. Worked out from its table, they match averages of the three repeat experiments. Short fibers of about 5 μm passed into a daughter cell, and division finished normally. Long fibers of about 20 μm bridged the two dividing cells and blocked the final splitting step, leaving cells with two nuclei. No statistical tests were done. No asbestos was tested in this study. The authors concluded that the mechanism was very similar to one observed with crocidolite asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell culture study using time-lapse live-cell imaging; published as a short report
• Who was studied: Cultured MDA-435 human breast cancer cells with fluorescently labeled chromosomes and centromeres. The experiment was run 3 times at each concentration, imaging 232, 112, 170 and 282 cells at 0, 12.7, 25.3 and 50.6 μg/mL respectively.
• Exposure: Multiwalled carbon nanotubes (MWCNT-7, Mitsui & Co.), about 100 nm in diameter, of which 27.5 % were at least 5 μm long. They were added to the culture medium at 0, 12.7, 25.3 or 50.6 μg/mL. No asbestos was tested.
• Main results:
  • Untreated (control) cells: 93 of 232 completed cell division and 4 died during cell division (printed as 40 % and 1.7 %).
  • Nanotube-treated cells at 12.7, 25.3 and 50.6 μg/mL: 40 of 112, 49 of 170 and 34 of 282 completed cell division, and 4, 11 and 21 died, respectively. The percentages printed (38 %, 27 %, 12 % and 3.2 %, 5.9 %, 7.6 %) match averages of the three repeat experiments in Table 1, not count divided by pooled total.
  • Binucleated cells in the treated groups: 0 of 112, 5 of 170 and 1 of 282 at 12.7, 25.3 and 50.6 μg/mL respectively (printed as 0 %, 3 % and 0.4 %).
  • Cells containing short fibers (about 5 μm) divided smoothly, like untreated cells, within 30 minutes.
  • Long fibers (about 20 μm) inhibited cytokinesis (the final splitting of a dividing cell) and induced the formation of binucleated cells.
  • During the 72-hour imaging period, no micronuclei or abnormal multipolar divisions attributable to the fibers were seen.
  • Uptake varied between cells: some ingested fibers within a few hours of exposure, and others did not.
• The authors' conclusion: The authors concluded that the way multiwalled carbon nanotubes induce binucleated cells is very similar to what has been observed with crocidolite. The crocidolite comparison relies on an earlier study by other researchers, not on crocidolite tested here.
• Limitations the authors state:
  • No statistical analysis was done on the rates of divided, dead or binucleated cells, because the imaged fields were deliberately chosen to contain many dividing cells.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Crocidolite, Genotoxicity.

Related studies

• A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro — T. Thurnherr, C. Brandenberger, et al. (2011)
• Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells — L. Tabet, C. Bussy, et al. (2009)
• Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells — K. Maruyama, H. Haniu, et al. (2015)
• Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure — L. Ju, W. Wu, et al. (2017)
• Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes — T.C. Vandivort, T.P. Birkland, et al. (2017)
• In vivo genotoxicity assessment of a multiwalled carbon nanotube in a mouse ex vivo culture — K. Horibata, H. Takasawa, et al. (2022)

Browse more research in Genes and Environment, or return to medical research.