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Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiationTo investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (<1.0 Gy); at higher doses (>1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.
Document ID
20040141936
Document Type
Reprint (Version printed in journal)
Authors
Limoli, C. L. (University of California San Francisco 94143-0750, United States)
Corcoran, J. J.
Milligan, J. R.
Ward, J. F.
Morgan, W. F.
Date Acquired
August 22, 2013
Publication Date
June 1, 1999
Publication Information
Publication: Radiation research
Volume: 151
Issue: 6
ISSN: 0033-7587
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: CA46295
CONTRACT_GRANT: GM 54189
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center