title: Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos.
abstract: Asbestos is a well-known occupational carcinogen that can cause aneuploidy during the early stages of neoplastic development. To explore the origins of asbestos-induced aneuploidy, we performed long-term live-cell imaging followed by fluorescence in situ hybridization of chromosomes 8 and 12 in human bronchial epithelial (HBEC) and mesothelial (MeT5A) cells. We demonstrate that asbestos induces aneuploidy via binucleated intermediates resulting from cytokinesis failure. On the one hand, asbestos increases chromosome nondisjunction during bipolar divisions of binucleated intermediates and produces near-tetraploidy. On the other hand, asbestos increases multipolar divisions of binucleated intermediates to produce aneuploidy. Surprisingly, chromosomes in asbestos-induced micronucleated cells are not truly lost by the cells, and do not contribute to aneuploid cell formation in either cell type. These results clarify the cellular source of asbestos-induced aneuploidy. In particular, they show the asbestos-induced disruption of bipolar chromosomal segregation in tetraploid cells, thereby demonstrating the causality between binucleated intermediates and aneuploidy evolution, rather than chromosome loss in micronuclei.
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ren
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230027, Anhui, China.|Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000782:Aneuploidy; D001194:Asbestos; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000235:genetics*; D002872:Chromosome Deletion; D020090:Chromosome Segregation / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000235:genetics*; D009630:Nondisjunction, Genetic / Q000235:genetics*; D008941:Spindle Apparatus / Q000235:genetics; D057891:Tetraploidy; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D001194:Asbestos
keywords: aneuploidy; asbestos; binucleated cell; chromosome nondisjunction; tetraploid