title: Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression.
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.
authors.affiliation: Depto Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.|Depto Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Beatriz Araujo
authors.initials: BA
authors.lastname: Cortez
authors.affiliation: Depto Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Paula
authors.initials: P
authors.lastname: Rezende-Teixeira
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Sambra
authors.initials: S
authors.lastname: Redick
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Doxsey
authors.affiliation: Depto Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Glaucia Maria
authors.initials: GM
authors.lastname: Machado-Santelli
mesh_terms: D000782:Aneuploidy; D017632:Asbestos, Serpentine / Q000494:pharmacology*; D064107:Aurora Kinase B / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008840:Microfilament Proteins / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D058112:Septins / Q000378:metabolism
chemical_list: C000591059:ANLN protein, human; D017632:Asbestos, Serpentine; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008840:Microfilament Proteins; C117020:PDCD6IP protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; C474315:SEPTIN9 protein, human; D058112:Septins
keywords: aneuploidy; chrysotile; cytokinesis regression; multipolar mitosis