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A possible role for centrosome overduplication in radiation-induced cell death

Oncogene volume 19, pages 5281–5290 (2000)Cite this article

Abstract

Radiotherapy plays a key role in the treatment of many tumors; however, the precise mechanisms responsible for radiation-induced cell death remain uncertain. We have reported previously that ionizing radiation induces centrosome overduplication in human tumor cells. The present study was designed to elucidate a possible link between centrosome dysregulation and radiation-induced cell death. Exposure to 10 Gy γ-radiation resulted in a substantial increase in cells containing an abnormally high number of centrosomes in a variety of cell lines derived from different types of human solid tumors. These aberrant centrosomes contribute to the assembly of multipolar spindles, thereby causing an unbalanced division of chromosomes and mitotic cell death characterized by the appearance of multi- or micronucleated cells. An extensive analysis of a panel of 10 tumor cell lines revealed a positive correlation between the fraction of cells with multiple centrosomes and the fraction with these nuclear abnormalities after irradiation. When the centrosome overduplication was blocked by enforced expression of p21Waf1/Cip1, the radiation-induced lethality was drastically rescued. Taken together, these results indicate that centrosome overduplication may be a critical event leading to mitotic failure and subsequent cell death following exposure to ionizing radiation.

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Acknowledgements

We thank Dr Masahiro Kusumoto and Ms Shoko Nishio for technical assistance. N Sato is a research fellow of the Japan Society for the Promotion of Science. This work was supported in part by a grant from the Ministry of Education, Science, and Culture of Japan.

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Authors and Affiliations

  1. Department of Surgery and Oncology, Gradulate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Norihiro Sato, Kazuhiro Mizumoto, Masafumi Nakamura, Yohji A Minamishima & Masao Tanaka

  2. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Hikaru Ueno

  3. Department of Pathology, Thomas Jefferson University, Philadelphia, 19017, Pennsylvania, PA, USA

    John L Farber

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  1. Norihiro Sato
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Sato, N., Mizumoto, K., Nakamura, M. et al. A possible role for centrosome overduplication in radiation-induced cell death. Oncogene 19, 5281–5290 (2000). https://doi.org/10.1038/sj.onc.1203902

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