title: Involvement of centrosome amplification in radiation-induced mitotic catastrophe.
abstract: Cells exposed to ionizing radiation die via different mechanisms, including apoptosis and mitotic catastrophe. To determine the frequency of mitotic catastrophe in tumor cells after irradiation, we used time-lapse imaging to track centrin-1 and histone H2B in U2OS osteosarcoma cells. We observed a dose-dependent increase in the frequency of mitotic catastrophe after irradiation, although a consistent 30% of cell death occurred through mitotic failure at doses from 2-10 Gy. One potential cause of mitotic catastrophe is centrosome amplification, which is induced by irradiation, and which can result in the formation of multipolar mitotic spindles. Up to 60% of mitotic catastrophes occurred in cells with >2 centrosomes after irradiation. We observed multipolar mitoses in p53(+) and p53(-) tumor cells after irradiation and found that the spindle assembly checkpoint is active in multipolar mitotic cells. However, we did not detect active caspase-3 in multipolar mitoses. These data demonstrate that a significant proportion of cell death induced by ionizing irradiation is through an apoptosis-independent mechanism involving centrosome amplification and mitotic catastrophe.
authors.affiliation: Department of Biochemistry and NCBES, National University of Ireland-Galway, Galway, Ireland.
authors.forename: Helen
authors.initials: H
authors.lastname: Dodson
authors.forename: Sally P
authors.initials: SP
authors.lastname: Wheatley
authors.forename: Ciaran G
authors.initials: CG
authors.lastname: Morrison
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D045325:HCT116 Cells; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018715:Microscopy, Video / Q000379:methods; D008938:Mitosis / Q000528:radiation effects*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3