Regular Article

British Journal of Cancer (2001) 84, 489–492. doi:10.1054/bjoc.2000.1604 www.bjcancer.com
Published online 13 February 2001

A role for chromosomal instability in the development of and selection for radioresistant cell variants

C L Limoli1, J J Corcoran2, R Jordan3, W F Morgan2 and J L Schwartz3

  1. 1Department of Radiation Oncology, University of California, San Francisco, CA 94103–0806, USA
  2. 2Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
  3. 3Department of Radiation Oncology, University of Washington, Seattle, WA, 98195, USA

Received 6 April 2000; Revised 19 October 2000; Accepted 27 October 2000.

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Abstract

Chromosome instability is a common occurrence in tumour cells. We examined the hypothesis that the elevated rate of mutation formation in unstable cells can lead to the development of clones of cells that are resistant to the cancer therapy. To test this hypothesis, we compared chromosome instability to radiation sensitivity in 30 independently isolated clones of GM10115 human–hamster hybrid cells. There was a broader distribution of radiosensitivity and a higher mean SF2in chromosomally unstable clones. Cytogenetic and DNA double-strand break rejoining assays suggest that sensitivity was a function of DNA repair efficiency. In the unstable population, the more radioresistant clones also had significantly lower plating efficiencies. These observations suggest that chromosome instability in GM10115 cells can lead to the development of cell variants that are more resistant to radiation. In addition, these results suggest that the process of chromosome breakage and recombination that accompanies chromosome instability might provide some selective pressure for more radioresistant variants. © 2001 Cancer Research Campaign

Keywords:

chromosome instability, radioresistance, DNA repair, radiation therapy

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