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HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animalsTransgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.
Document ID
20040088543
Acquisition Source
Goddard Space Flight Center
Document Type
Reprint (Version printed in journal)
Authors
Chang, P. Y.
(SRI International, Menlo Park, CA 94025, United States)
Kanazawa, N.
Lutze-Mann, L.
Winegar, R.
Date Acquired
August 21, 2013
Publication Date
January 1, 2001
Publication Information
Publication: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)
Volume: 17 Suppl 1
ISSN: 1120-1797
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: NAG5-6177
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Radiation Health

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