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clustered dna damages induced in isolated dna and in human cells by low doses of ionizing radiationClustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.
Document ID
20040141721
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Sutherland, B. M.
(Brookhaven National Laboratory Upton, NY 11973-5000, United States)
Bennett, P. V.
Sidorkina, O.
Laval, J.
Lowenstein, D. I.
Date Acquired
August 22, 2013
Publication Date
January 4, 2000
Publication Information
Publication: Proceedings of the National Academy of Sciences of the United States of America
Volume: 97
Issue: 1
ISSN: 0027-8424
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center