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

Abstract

IntroductionAsbestos-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.FindingsDuring 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.ConclusionsOur findings indicate that the mechanism of polyploidization by MWCNTs is very similar to that observed with crocidolite.Electronic supplementary materialThe online version of this article (doi:10.1186/s41021-015-0003-y) contains supplementary material, which is available to authorized users.

Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure

“…MWCNT has been linked to asbestos in terms of morphology and toxicity, which could lead to lung cancer or even mesothelioma [ 4 , 13 ], but contradictory findings coexist. Possible explanations include the different cell systems, varied types of commercial MWCNTs, different detection time points, and different MWCNT concentrations applied in these studies.…”

“…Moreover, after long-term treatments, MeT-5A cell morphology was also changed to be smaller and round in shape, which is consistent with the results for human lung epithelial BEAS-2B cells after exposure to single-walled carbon nanotube [ 18 ]. It has been reported that MWCNT-induced formation of polyploidization and aneuploidization may be attributed to the cell morphology changes [ 13 ]. In our earlier study, MWCNT caused increased expression of actin as well as actin filament remodeling in A549 cells, which may be another reason for the morphology change [ 12 ].…”

Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment

“…Asakura et al 61) also reported increased numbers of bi- and multi-nucleated cells without micronucleus induction. Yasui et al 62) observed that comparatively long MWNT-7 (approximately ≥ 20 μm) inhibited cytokinesis during cell division and induced the formation of bi-nucleated cells, whereas short MWNT-7 did not. In addition, Kato et al 63) reported that MWNT-7 induced micronucleus formation and sister chromatid exchange.…”

Absence of in vivo mutagenicity of multi-walled carbon nanotubes in single intratracheal instillation study using F344 gpt delta rats

“…060125-01 k, Mitsui & Co., Ltd., Ibaraki, Japan) were prepared as described previously [4, 5, 26], with some modifications. According to the reports, these straight MWCNT fibers are approximately 100 nm in diameter, and 27.5% of the MWCNTs are ≥ 5 μm in length.…”