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Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2

Oncogene volume 18, pages 7334–7342 (1999)Cite this article

Abstract

There is now evidence to suggest that BRCA1 and BRCA2 are involved in the response of cells to DNA damage and cell cycle checkpoint control. This report examines the death pathways of human cells with various BRCA1 and BRCA2 genotypes after exposure to gamma-rays. A lack of functional BRCA1 and BRCA2 led to defective repair of DNA double-strand breaks in irradiated cells. This impairment resulted in a relaxation of cell cycle checkpoints, production of micronuclei, and a loss of proliferative capacity. Heterozygous BRCA1 and BRCA2 mutations also led to enhanced radiosensitivity, with an impaired proliferative capacity after irradiation. The existence of a phenotype related to radiosensitivity in BRCA1+/− and BRCA2+/− cells raises the question of the response of heterozygous women to radiation.

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Acknowledgements

We thank Arlette Vervisch (Cytometry laboratory – CNRS) for her excellent technical assistance in cell cycle analysis. Dr Agnès Hardouin is gratefully acknowledged for communicating the status of BRCA1 in the IGROV1 cell line prior to publication. This work was supported by a Contrat Libre (No. 9023) from ARC. N Foray was supported by post-doctoral fellowships from the Ligue Nationale Contre le Cancer and from Electricité de France (Département de Radioprotection).

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Authors and Affiliations

  1. Laboratoire de Génétique Oncologique, CNRS UMR #1599, Institut Gustave-Roussy, 94805 Villejuif Cedex, France

    Nicolas Foray & Jean Feunteun

  2. Laboratoire de Vectorologie et Transfert de gènes, CNRS UMR #1582, Institut Gustave-Roussy, 94805 Villejuif Cedex, France

    Voahangy Randrianarison, Didier Marot & Michel Perricaudet

  3. Laboratoire de Génétique et Cancer, CNRS UMR #5641, Université LYON 1, 8 Avenue Rockfeller, Lyon, France

    Gilbert Lenoir

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  1. Nicolas Foray
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Foray, N., Randrianarison, V., Marot, D. et al. Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2. Oncogene 18, 7334–7342 (1999). https://doi.org/10.1038/sj.onc.1203165

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