Involvement of centrosome amplification in radiation-induced mitotic catastrophe

Cell Cycle. 2007 Feb 1;6(3):364-70. doi: 10.4161/cc.6.3.3834. Epub 2007 Feb 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Centrosome / metabolism*
  • Centrosome / radiation effects
  • Dose-Response Relationship, Radiation
  • HCT116 Cells
  • Humans
  • Immunoblotting
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Microscopy, Video / methods
  • Mitosis / radiation effects*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / radiation effects
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Calcium-Binding Proteins
  • Luminescent Proteins
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • Caspase 3