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H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

Vasireddy, RS; Sprung, CN; Cempaka, NL; Chao, M; McKay, Michael

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Background:About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as γH2AX) occurs rapidly in response to DNA DSBs, and, among its other...[Show more]

dc.contributor.authorVasireddy, RS
dc.contributor.authorSprung, CN
dc.contributor.authorCempaka, NL
dc.contributor.authorChao, M
dc.contributor.authorMcKay, Michael
dc.date.accessioned2015-12-10T23:00:59Z
dc.identifier.issn0007-0920
dc.identifier.urihttp://hdl.handle.net/1885/61574
dc.description.abstractBackground:About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as γH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS).Methods:Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by γH2AX foci assays, as potential predictive markers of clinical radiation response.Results:With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using γH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay.Conclusion:γH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS.
dc.publisherNature Publishing Group
dc.sourceBritish Journal of Cancer
dc.subjectKeywords: DNA; double stranded DNA; histone H2AX; adult; aged; article; cancer cell culture; cancer localization; cancer patient; cancer radiotherapy; cancer screening; cell regeneration; clinical article; controlled study; DNA strand breakage; female; human; human ?; H2AX; Ionising radiation; Radiosensitivity
dc.titleH2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume102
dc.date.issued2010
local.identifier.absfor111299 - Oncology and Carcinogenesis not elsewhere classified
local.identifier.ariespublicationf2965xPUB622
local.type.statusPublished Version
local.contributor.affiliationVasireddy, RS, University of Melbourne
local.contributor.affiliationSprung, CN, University of Melbourne
local.contributor.affiliationCempaka, NL, University of Melbourne
local.contributor.affiliationChao, M, University of Melbourne
local.contributor.affiliationMcKay, Michael, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue10
local.bibliographicCitation.startpage1511
local.bibliographicCitation.lastpage1518
local.identifier.doi10.1038/sj.bjc.6605666
dc.date.updated2016-02-24T08:31:02Z
local.identifier.scopusID2-s2.0-77952116482
CollectionsANU Research Publications

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