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• W401577125 abstract "Following a radiological or nuclear disaster, radiation dose assessment is imperativeto minimize morbidity and mortality through rationally directed medical intervention.Current methods of retrospective dosimetry are not amenable to mass exposure scenariosand remain limited to monitoring of clinical symptoms (nausea/vomiting and lymphocytedepletion) and cytogenetic analysis. The goal of this study was to identify radiationbiomarkers capable of qualitative (non-irradiated/irradiated) and quantitative (dose)assessment of radiation exposure. Initial analyses revealed 17 radiation-responsive cytokine/chemokine genes in blood samples from 6 pediatric cancer patients undergoing fractionatedtotal body irradiation (TBI). These 17 genes were combined with 29 additionalIR-inducible genes (46 genes total) identified in the literature to formulate a rationallydesigned Taqman Low Density Array (TLDA) for subsequent studies. TLDA analysiswas performed in blood samples from 9 healthy volunteers and from 4 additional patientsat baseline and 5, 23, and 48 hours following the initial 2 Gy fraction of TBI. Of these 46genes, 8 demonstrated increased expression post-TBI, with no significant differences betweenvolunteers and baseline patient samples. These 8 genes were examined in C57BL6mice at 0, 5, 12, 23, and 48 hours post-TBI (0, 1, 2, or 6 Gy). There were significant increasesin Bbc3, Ccng1, Cdkn1a, Serpine1, and Tnfrsf10b post-TBI as well as lineardose-dependent responses at 48 hours. A weighted voting algorithm followed by leaveone-out cross validation was utilized to identify molecular signatures capable of accuivrately classifying mice as exposed versus not exposed. At 48 hours, expression of Ccng1and Cdkn1a correctly classified mice with an accuracy of 92.6%. Testing of this modelin an independent validation set of mice (exposed to 0, 1, 2, 4, 6, or 8 Gy) revealed 96.3%accuracy in segregating mice into correct exposure categories. Multiple linear regressionanalysis at 48 hours using these same two genes predicted doses for the 0, 1, 2, 4, 6, and 8Gy treatment groups as 0.0±0.2, 1.6±1.0, 2.9±1.4, 5.1±2.0, 5.3±0.7, and 10.5±5.6 Gy,respectively. These studies suggest that incorporation of gene expression analysis intocurrent biodosimetry protocols may facilitate triage of exposed individuals and directtreatment decisions.%%%%1 online resource (xii, 109 p. : ill., digital, PDF file)%%%%%%%%Pharmacology and Toxicology;%%%%Joint Health Sciences;%%%%total body irradiation biodosimetry radiation weighted voting analysis%%%%UNRESTRICTED" @default.
• W401577125 created "2016-06-24" @default.
• W401577125 creator A5073703386 @default.
• W401577125 date "2010-01-01" @default.
• W401577125 modified "2023-09-23" @default.
• W401577125 title "Identification and validation of biodosimetry markers in multiple models of radiation exposure" @default.
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• W401577125 hasPublicationYear "2010" @default.
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