title: Gene expression analysis in radiotherapy patients and C57BL/6 mice as a measure of exposure to ionizing radiation.
abstract: Dose assessment after radiological disasters is imperative to decrease mortality through rationally directed medical intervention. Our goal was to identify biomarkers capable of qualitative (nonirradiated/irradiated) and/or quantitative (dose) assessment of radiation exposure. Using real-time quantitative PCR, biodosimetry genes were identified in blood samples from cancer patients undergoing total-body irradiation. Time- (5, 12, 23, 48 h) and dose- (0-8 Gy) dependent changes in gene expression were examined in C57BL/6 mice. A training set was used to derive weighted voting classification algorithms (nonirradiated/irradiated) and continuous regression (dose assessment) models that were tested in a separate validation set of mice. Of eight biodosimetry genes identified in cancer patients ( ACTA2 , BBC3 , CCNG1 , CDKN1A , GADD45A , MDK , SERPINE1 , Tnfrsf10b ), expression of BBC3 , CCNG1 , CDKN1A , SERPINE1 and Tnfrsf10b was significantly (P < 0.05) increased in irradiated mice. CCNG1 and CDKN1A expression segregated irradiated mice from controls with an accuracy, specificity and sensitivity of 96.3, 100.0 and 94.4%, respectively, at 48 h. Multiple linear regression analysis predicted doses for the 0-, 1-, 2-, 4-, 6- and 8-Gy 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 results suggest that gene expression analysis could be incorporated into biodosimetry protocols for qualitative and quantitative assessment of radiation exposure.
authors.affiliation: Department of Pharmacology and Toxicology, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Filiano
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Fathallah-Shaykh
authors.forename: John
authors.initials: J
authors.lastname: Fiveash
authors.forename: Jarrod
authors.initials: J
authors.lastname: Gage
authors.forename: Alan
authors.initials: A
authors.lastname: Cantor
authors.forename: Sandhya
authors.initials: S
authors.lastname: Kharbanda
authors.forename: Martin R
authors.initials: MR
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000532:radiotherapy*; D011833:Radiation Injuries, Experimental / Q000235:genetics*; D011839:Radiation, Ionizing; D011874:Radiometry / Q000379:methods*; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects; D055815:Young Adult