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

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 mu m) migrated rapidly to either of the daughter cells, whereas some long MWCNT fibers (approximately 20 mu m) 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.