Involvement of Centrosome Amplification in Radiation-Induced Mitotic Catastrophe

Helen Dodson, Sally P. Wheatley and Ciaran Morrison

volume 6 | issue 3

1 February 2007
Pages: 364 - 370

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Cells exposed to ionising radiation die via different mechanisms, including apoptosis and mitotic catastrophe. To determine the frequency of mitotic catastrophe in tumour cells after irradiation, we used timelapse 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- tumour 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 ionising irradiation is through an apoptosis-independent mechanism involving centrosome amplification and mitotic catastrophe.

Authors

Helen Dodson

National University of Ireland, Galway, Ireland

Sally P. Wheatley

University of Sussex, Brighton, UK

Ciaran Morrison

National University of Ireland Galway

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: