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

// Beatriz Araujo Cortez 1,2 , Paula Rezende Teixeira 1 , Sambra Redick 3 , Stephen Doxsey 3 and Glaucia Maria Machado-Santelli 1 1 Depto Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brasil 2 Depto Genetica e Biologia Evolutiva, Instituto de Biociencias, Universidade de Sao Paulo, Sao Paulo, Brasil 3 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA Correspondence to: Beatriz Araujo Cortez, email: // Keywords : chrysotile, cytokinesis regression, multipolar mitosis, aneuploidy Received : August 31, 2015 Accepted : January 03, 2016 Published : January 15, 2016 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.