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Processing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cells

dc.contributor.authorGeorgakilas, Alexandros G.en_US
dc.contributor.authorBennett, Paula V.en_US
dc.contributor.authorWilson III, David M.en_US
dc.contributor.authorSutherland, Betsy M.en_US
dc.date.accessioned2010-11-17T19:35:33Zen_US
dc.date.accessioned2011-05-17T14:35:03Z
dc.date.available2010-11-17T19:35:33Zen_US
dc.date.available2011-05-17T14:35:03Z
dc.date.issued2004en_US
dc.description.abstractClustered DNA damages—two or more lesions on opposing strands and within one or two helical turns—are formed in cells by ionizing radiation or radiomimetic antitumordrugs. They are hypothesized to be difficult to repair, and thus are critical biological damages. Since individual abasic sites can be cytotoxic or mutagenic, abasicDNAclusters are likely to have significant cellular impact. Using a novel approach for distinguishing abasic clusters that are very closely spaced (putrescine cleavage) or less closely spaced (Nfo protein cleavage), we measured induction and processing of abasic clusters in 28SC human monocytes that were exposed to ionizing radiation. g-rays induced 1 double-strand break: 1.3 putrescine-detected abasic clusters: 0.8 Nfodetected abasic clusters. After irradiation, the 28SC cells rejoined double-strand breaks efficiently within 24 h. In contrast, in these cells, the levels of abasic clusters decreased very slowly over 14 days to background levels. In vitro repair experiments that used 28SC cell extracts further support the idea of slow processing of specific, closely spaced abasic clusters. Although some clusters were removed by active cellular repair, a substantial number was apparently decreased by ‘splitting’ during DNA replication and subsequent cell division. The existence of abasic clusters in 28SC monocytes, several days after irradiation suggests that they constitute persistent damages that could lead to mutation or cell killing. Originally published in Nucleic Acids Research 2004 Vol. 32, No. 18.en_US
dc.identifier.citationNucleic Acids Research; 32:18 p. 5609-5620en_US
dc.identifier.pmidPMC524283en_US
dc.identifier.urihttp://hdl.handle.net/10342/3003en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://nar.oxfordjournals.org/content/32/18.tocen_US
dc.rightsPermission granted by author to Kent Nixon Myers to upload this article on 11/04/2010.en_US
dc.titleProcessing of bistranded abasic DNA clusters in γ-irradiated human hematopoietic cellsen_US
dc.typeArticleen_US

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