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Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytesTransgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.
Document ID
20040112612
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Chang, P. Y.
(PN147, SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025, United States)
Torous, D.
Lutze-Mann, L.
Winegar, R.
Date Acquired
August 21, 2013
Publication Date
March 3, 2000
Publication Information
Publication: Mutation research
Volume: 466
Issue: 1
ISSN: 0027-5107
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
NASA Program Biomedical Research and Countermeasures
Non-NASA Center

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