title: Gene expression-based dosimetry by dose and time in mice following acute radiation exposure.
abstract: Rapid and reliable methods for performing biological dosimetry are of paramount importance in the event of a large-scale nuclear event. Traditional dosimetry approaches lack the requisite rapid assessment capability, ease of use, portability and low cost, which are factors needed for triaging a large number of victims. Here we describe the results of experiments in which mice were acutely exposed to (60)Co gamma rays at doses of 0 (control) to 10 Gy. Blood was obtained from irradiated mice 0.5, 1, 2, 3, 5, and 7 days after exposure. mRNA expression levels of 106 selected genes were obtained by reverse-transcription real time PCR. Stepwise regression of dose received against individual gene transcript expression levels provided optimal dosimetry at each time point. The results indicate that only 4-7 different gene transcripts are needed to explain ≥ 0.69 of the variance (R(2)), and that receiver-operator characteristics, a measure of sensitivity and specificity, of ≥ 0.93 for these statistical models were achieved at each time point. These models provide an excellent description of the relationship between the actual and predicted doses up to 6 Gy. At doses of 8 and 10 Gy there appears to be saturation of the radiation-response signals with a corresponding diminution of accuracy. These results suggest that similar analyses in humans may be advantageous for use in a field-portable device designed to assess exposures in mass casualty situations.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: James D
authors.initials: JD
authors.lastname: Tucker
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: George W
authors.initials: GW
authors.lastname: Divine
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Grever
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Thomas
authors.affiliation: Department of Radiation Oncology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
authors.affiliation: Department of Electrical and Computer Engineering, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Smolinski
authors.affiliation: Department of Electrical and Computer Engineering, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Auner
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005720:Gamma Rays; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D013997:Time Factors