DOI: 10.1073/pnas.97.1.103. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

10.1073/pnas.97.1.103

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Clustered 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.

Bibliography

Sutherland, B. M., Bennett, P. V., Sidorkina, O., & Laval, J. (2000). Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation. Proceedings of the National Academy of Sciences, 97(1), 103â108.

Authors 4

Betsy M. Sutherland (first)
Paula V. Bennett (additional)
Olga Sidorkina (additional)
Jacques Laval (additional)

References 52 Referenced 382

M J Bissell, H W Warner, S M Berget, R J M Fry, P C Hanawalt, M Kastan, A Kornberg, L Lutze-Mann, K A Souza, R Ullrich, et al. Modeling Human Risk: Cell and Molecular Biology in Context (Lawrence Berkeley National Laboratory, Univ. of California, Berkeley, 1997). / Modeling Human Risk: Cell and Molecular Biology in Context by Bissell M J (1997)
Yang T. C. George K. Johnson A. S. Durante M. & Fedorendo B. S. (1997) Radiat. Res. 148 (5 Suppl.) S17–S23. (10.2307/3579712)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:18 p.m.)
Indexed	1 week ago (Aug. 29, 2025, 6:02 a.m.)
Issued	25 years, 8 months ago (Jan. 4, 2000)
Published	25 years, 8 months ago (Jan. 4, 2000)
Published Online	25 years, 8 months ago (Jan. 4, 2000)
Published Print	25 years, 8 months ago (Jan. 4, 2000)

Funders 0

None

BibTeX

@article{Sutherland_2000, title={Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.97.1.103}, DOI={10.1073/pnas.97.1.103}, number={1}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sutherland, Betsy M. and Bennett, Paula V. and Sidorkina, Olga and Laval, Jacques}, year={2000}, month=jan, pages={103–108} }

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