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Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous miceAtaxia-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.
Document ID
20040112350
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Weil, M. M.
(The University of Texas MD Anderson Cancer Center Houston, Texas, TX 77030-4095, United States)
Kittrell, F. S.
Yu, Y.
McCarthy, M.
Zabriskie, R. C.
Ullrich, R. L.
Date Acquired
August 21, 2013
Publication Date
July 19, 2001
Publication Information
Publication: Oncogene
Volume: 20
Issue: 32
ISSN: 0950-9232
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: CA43322
CONTRACT_GRANT: CA06294
CONTRACT_GRANT: CA73929
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Radiation Health

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