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Lymphoid and fibroblastic cell lineages from radiosensitive cancer patients: Molecular analysis of DNA double strand break repair by major non-homologous end-joining sub-pathways

McKay, Michael; WITHANA, Nimali; DAVEY, Deborah; Bishop, Danial; Chao, Michael; Sprung, Carl N.

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Aims: Radiation therapy (RT) is used in the treatment of approximately half of all cancer patients. Although there have been great improvements in tumor localization and the technical accuracy of RT delivery, some RT patients still have idiosyncratic hypersensitivity to ionizing radiation (IR) in their normal tissues. Although much effort has been expended in the search for assays that could detect radiosensitive individuals prior to treatment and facilitate tailored therapy; a suitable and...[Show more]

dc.contributor.authorMcKay, Michael
dc.contributor.authorWITHANA, Nimali
dc.contributor.authorDAVEY, Deborah
dc.contributor.authorBishop, Danial
dc.contributor.authorChao, Michael
dc.contributor.authorSprung, Carl N.
dc.date.accessioned2015-12-10T23:24:40Z
dc.identifier.issn1743-7563
dc.identifier.urihttp://hdl.handle.net/1885/67297
dc.description.abstractAims: Radiation therapy (RT) is used in the treatment of approximately half of all cancer patients. Although there have been great improvements in tumor localization and the technical accuracy of RT delivery, some RT patients still have idiosyncratic hypersensitivity to ionizing radiation (IR) in their normal tissues. Although much effort has been expended in the search for assays that could detect radiosensitive individuals prior to treatment and facilitate tailored therapy; a suitable and clinically practical predictive assay has yet to be realized. Since DNA double-strand breaks (DSB) are a major lesion caused by IR, we hypothesized that radiation hypersensitive individuals might be deficient in the repair of such lesions. Methods: To test this hypothesis we quantitatively and functionally characterized DSB repair of the two major non-homologous end-joining (NHEJ) sub-pathways in a pilot study using a plasmid repair reconstitution assay in lymphoblastoid and fibroblast cell lines from radiosensitive cancer patients and controls. Experiments using well-characterized mammalian DSB repair mutants demonstrated the ability of the assay to distinguish NHEJ sub-pathways. The proportion of direct end-joining repair compared with that of microhomology-directed repair was used as a functional end-point of DSB repair competence in the different cell lines. Results: We found that the overall level of NHEJ sub-pathway repair competency was similar in cell lines from radiosensitive patients and controls. Conclusion: These data suggest that this assay in these cell lineages has limited usefulness as a predictive screen for the endogenous DNA DSB repair competency of radiosensitive cancer patients' cells but can usefully characterize major cellular DSB repair phenotypes.
dc.publisherBlackwell Publishing Ltd
dc.sourceAsia-Pacific Journal of Clinical Oncology
dc.subjectKeywords: complementary DNA; double stranded DNA; article; bladder mucosa; breast cancer; cancer patient; cancer radiotherapy; CHO cell; clinical article; controlled study; DNA sequence; DNA strand breakage; female; fibroblast; histology; human; human cell; lymphoi Fibroblast; Lymphoblast; Microhomology; Non-homologous end-joining; Predictive assay; Radiosensitivity
dc.titleLymphoid and fibroblastic cell lineages from radiosensitive cancer patients: Molecular analysis of DNA double strand break repair by major non-homologous end-joining sub-pathways
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume7
dc.date.issued2011
local.identifier.absfor111208 - Radiation Therapy
local.identifier.ariespublicationf2965xPUB1432
local.type.statusPublished Version
local.contributor.affiliationMcKay, Michael, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWITHANA, Nimali, Peter MacCallum Cancer Centre
local.contributor.affiliationDAVEY, Deborah, Peter MacCallum Cancer Centre
local.contributor.affiliationBishop, Danial, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChao, Michael, Royal Melbourne Hospital
local.contributor.affiliationSprung, Carl N., Monash University
local.description.embargo2037-12-31
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage17
local.bibliographicCitation.lastpage26
local.identifier.doi10.1111/j.1743-7563.2010.01364.x
local.identifier.absseo970111 - Expanding Knowledge in the Medical and Health Sciences
dc.date.updated2016-02-24T08:13:50Z
local.identifier.scopusID2-s2.0-79951752958
CollectionsANU Research Publications

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