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Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

Oncogene volume 20, pages 4409–4411 (2001)Cite this article

Abstract

Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm+/+ mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

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Acknowledgements

We wish to thank D Medina, M Stovall, B Brown and M Bondy for helpful discussions, K Mason for assistance with the mouse surgeries and W Pagel for editorial assistance. This work was supported by NIH Grants CA06294, CA73929 and CA43322.

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Authors and Affiliations

  1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030-4095, Texas, TX, USA

    Michael M Weil

  2. Department of Cell Biology, Baylor College of Medicine, Houston, 77030-3411, Texas, TX, USA

    Frances S Kittrell

  3. Department of Radiation Oncology, Biology Division, The University of Texas Medical Branch at Galveston, Galveston, 77555-0656, Texas, TX, USA

    Yongjia Yu, Maureen McCarthy & Ryan C Zabriskie

  4. Department of Radiological Health Sciences, Colorado State University, Fort Collins, 80523-1673, Colorado, CO, USA

    Robert L Ullrich

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  1. Michael M Weil
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Correspondence to Michael M Weil.

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Weil, M., Kittrell, F., Yu, Y. et al. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. Oncogene 20, 4409–4411 (2001). https://doi.org/10.1038/sj.onc.1204589

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