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dc.contributor.authorCruz-Garcia, L
dc.contributor.authorO'Brien, G
dc.contributor.authorDonovan, E
dc.contributor.authorGothard, L
dc.contributor.authorBoyle, S
dc.contributor.authorLaval, A
dc.contributor.authorTestard, I
dc.contributor.authorPonge, L
dc.contributor.authorWoźniak, G
dc.contributor.authorMiszczyk, L
dc.contributor.authorCandéias, SM
dc.contributor.authorAinsbury, E
dc.contributor.authorWidlak, P
dc.contributor.authorSomaiah, N
dc.contributor.authorBadie, C
dc.date.accessioned2018-01-30T11:32:25Z
dc.date.accessioned2019-02-25T10:06:05Z
dc.date.issued2018-07-01
dc.identifier.citationHealth physics, 2018, 115 (1), pp. 90 - 101
dc.identifier.issn0017-9078
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3081
dc.identifier.eissn1538-5159
dc.identifier.doi10.1097/hp.0000000000000844
dc.description.abstractFor triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti-inflammatory/antioxidant agent. Their potential influence on the transcriptional response to radiation of the genes CCNG1 and PHPT1, two biomarkers of radiation exposure ex vivo, was assessed. First, both CCNG1 and PHPT1 were detected in vivo in blood samples from radiotherapy patients and as such were validated as biomarkers of exposure. Importantly, their basal expression level was slightly but significantly affected in vivo by patients' cancer condition. Moreover, lipopolysaccharide stimulation of blood irradiated ex vivo led to a significant modification of CCNG1 and PHPT1 transcriptional response in a dose- and time-dependent manner with opposite regulatory effects. Curcumin also affected CCNG1 and PHPT1 transcriptional response counteracting some of the radiation induction. No differences were observed based on sex. Dose estimations calculated using linear regression were affected by lipopolysaccharide and curcumin. In conclusion, several confounding factors tested in this study can indeed modulate the transcriptional response of CCNG1 and PHPT1 and consequently can affect radiation exposure dose estimations but not to a level which should prevent the biomarkers' use for triage purposes.
dc.formatPrint
dc.format.extent90 - 101
dc.languageeng
dc.language.isoeng
dc.publisherLIPPINCOTT WILLIAMS & WILKINS
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/1034
dc.relation.replacesinternal/1034
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectCurcumin
dc.subjectPhosphoric Monoester Hydrolases
dc.subjectLipopolysaccharides
dc.subjectAntineoplastic Agents
dc.subjectRadiotherapy Dosage
dc.subjectCase-Control Studies
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectRadiotherapy, Intensity-Modulated
dc.subjectCyclin G1
dc.subjectBiomarkers
dc.titleInfluence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers.
dc.typeJournal Article
dcterms.dateAccepted2018-01-29
rioxxterms.versionofrecord10.1097/hp.0000000000000844
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfHealth physics
pubs.issue1
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Yarnold)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Breast Radiobiology
pubs.publication-statusPublished
pubs.volume115
pubs.embargo.termsNo embargo
icr.researchteamClinical Academic Radiotherapy (Yarnold)
icr.researchteamTranslational Breast Radiobiology
dc.contributor.icrauthorGothard, Lone
dc.contributor.icrauthorBoyle, Susan
dc.contributor.icrauthorSomaiah, Navita


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