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Radioprotection of Human Cell Nuclear DNA by Polyamines: Radiosensitivity of Chromatin is Influenced by Tightly Bound SpermineThe polyamines putrescine (PUT) and spermine (SPM) were examined for their ability to protect human cell Deoxyribonucleic Acid (DNA) against the formation of radiation-induced double-strand breaks (DSBs). As observed previously, under conditions where polyamines were shown to be almost completely absent, association with nuclear matrix protein into a nucleoid, and organization into chromatin structure, protected DNA from induction of DSBs by factors of 4.5 and 95, respectively. At concentrations below 1 mM, PUT or SPM provided equivalent levels of protection to deproteinized nuclear DNA, consistent with their capacity to scavenge radiation-induced radicals. At constant ionic strength, 5 mM SPM protected deproteinized DNA and nucleoid DNA and DNA in nuclear chromatin by factors of 100 and 26, respectively. At 5 mM, SPM provided 15 times greater protection of deproteinized DNA than did PUT. Under physiologically relevant conditions, 5 mM SPM protected DNA in the intact nucleus from the induction of DSBs by a factor of 2 relative to DNA in the absence of SPM. Studies of SPM binding during cellular fractionation revealed that a significant fraction of the cellular SPM is tightly bound in the nucleus but can be removed by extended washing. Thus the association of SPM with nuclear chromatin appears to be a significant contributor to the resistance of the cell's DNA to the induction of DSBs.
Document ID
20000109863
Acquisition Source
Headquarters
Document Type
Reprint (Version printed in journal)
Authors
Warters, Raymond L.
(Utah Univ. Salt Lake City, UT United States)
Newton, Gerald L.
(California Univ., San Diego La Jolla, CA United States)
Olive, Peggy L.
(British Columbia Univ. Vancouver, British Columbia Canada)
Fahey, Robert C.
(California Univ., San Diego La Jolla, CA United States)
Date Acquired
August 19, 2013
Publication Date
January 1, 1999
Publication Information
Publication: Radiation Research
Publisher: Radiation Research Society
Volume: 151
ISSN: 0033-7587
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: NIH-5P30-CA-42014
CONTRACT_GRANT: NAGW-4914
CONTRACT_GRANT: NIH-NCI-CA-35982
Distribution Limits
Public
Copyright
Other

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