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dc.contributor.authorLowe, Donna Jen
dc.contributor.authorHerzog, Mareikeen
dc.contributor.authorMosler, Thorstenen
dc.contributor.authorCohen, Howarden
dc.contributor.authorFelton, Sarahen
dc.contributor.authorBeli, Petraen
dc.contributor.authorRaj, Kenen
dc.contributor.authorGalanty, Yaronen
dc.contributor.authorJackson, Stephenen
dc.date.accessioned2020-02-06T00:30:32Z
dc.date.available2020-02-06T00:30:32Z
dc.date.issued2020-02-10en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301759
dc.description.abstractOver the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6-20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherNature Publishing Group
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectCell Lineen
dc.subjectChromatinen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectDNA Damageen
dc.subjectHistonesen
dc.subjectDNAen
dc.subjectDose-Response Relationship, Radiationen
dc.subjectCell Proliferationen
dc.subjectDNA Repairen
dc.subjectGene Expressionen
dc.subjectGamma Raysen
dc.subjectMaleen
dc.subjectDNA Breaks, Double-Strandeden
dc.subjectPrimary Cell Cultureen
dc.subjectCellular Senescenceen
dc.titleChronic irradiation of human cells reduces histone levels and deregulates gene expression.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2020en
prism.publicationNameScientific reportsen
prism.startingPage2200
prism.volume10en
dc.identifier.doi10.17863/CAM.48833
dcterms.dateAccepted2020-01-24en
rioxxterms.versionofrecord10.1038/s41598-020-59163-4en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-02-10en
dc.contributor.orcidHerzog, Mareike [0000-0001-9747-2327]
dc.contributor.orcidFelton, Sarah [0000-0003-3304-0490]
dc.contributor.orcidBeli, Petra [0000-0001-9507-9820]
dc.contributor.orcidGalanty, Yaron [0000-0001-7167-9004]
dc.contributor.orcidJackson, Stephen [0000-0001-9317-7937]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (A18796)
pubs.funder-project-idWellcome Trust (206388/Z/17/Z)
pubs.funder-project-idCancer Research UK (C6946/A24843)
pubs.funder-project-idWellcome Trust (203144/Z/16/Z)
cam.orpheus.successMon Jun 08 08:19:38 BST 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2023-02-05


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