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Oncotarget. 2016 Feb 23;7(8):8979-92. doi: 10.18632/oncotarget.6924.

Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression.

Author information

1
Depto Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.
2
Depto Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
3
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.

Abstract

Chrysotile, like other types of asbestos, has been associated with mesothelioma, lung cancer and asbestosis. However, the cellular abnormalities induced by these fibers involved in cancer development have not been elucidated yet. Previous works show that chrysotile fibers induce features of cancer cells, such as aneuploidy, multinucleation and multipolar mitosis. In the present study, normal and cancer derived human cell lines were treated with chrysotile and the cellular and molecular mechanisms related to generation of aneuploid cells was elucidated. The first alteration observed was cytokinesis regression, the main cause of multinucleated cells formation and centrosome amplification. The multinucleated cells formed after cytokinesis regression were able to progress through cell cycle and generated aneuploid cells after abnormal mitosis. To understand the process of cytokinesis regression, localization of cytokinetic proteins was investigated. It was observed mislocalization of Anillin, Aurora B, Septin 9 and Alix in the intercellular bridge, and no determination of secondary constriction and abscission sites. Fiber treatment also led to overexpression of genes related to cancer, cytokinesis and cell cycle. The results show that chrysotile fibers induce cellular and molecular alterations in normal and tumor cells that have been related to cancer initiation and progression, and that tetraploidization and aneuploid cell formation are striking events after fiber internalization, which could generate a favorable context to cancer development.

KEYWORDS:

aneuploidy; chrysotile; cytokinesis regression; multipolar mitosis

PMID:
26788989
PMCID:
PMC4891019
DOI:
10.18632/oncotarget.6924
[Indexed for MEDLINE]
Free PMC Article

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