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Title: Accurate Gene Expression-Based Biodosimetry Using a Minimal Set of Human Gene Transcripts

Purpose: Rapid and reliable methods for conducting biological dosimetry are a necessity in the event of a large-scale nuclear event. Conventional biodosimetry methods lack the speed, portability, ease of use, and low cost required for triaging numerous victims. Here we address this need by showing that polymerase chain reaction (PCR) on a small number of gene transcripts can provide accurate and rapid dosimetry. The low cost and relative ease of PCR compared with existing dosimetry methods suggest that this approach may be useful in mass-casualty triage situations. Methods and Materials: Human peripheral blood from 60 adult donors was acutely exposed to cobalt-60 gamma rays at doses of 0 (control) to 10 Gy. mRNA expression levels of 121 selected genes were obtained 0.5, 1, and 2 days after exposure by reverse-transcriptase real-time PCR. Optimal dosimetry at each time point was obtained by stepwise regression of dose received against individual gene transcript expression levels. Results: Only 3 to 4 different gene transcripts, ASTN2, CDKN1A, GDF15, and ATM, are needed to explain ≥0.87 of the variance (R{sup 2}). Receiver-operator characteristics, a measure of sensitivity and specificity, of 0.98 for these statistical models were achieved at each time point. Conclusions: The actual and predictedmore » radiation doses agree very closely up to 6 Gy. Dosimetry at 8 and 10 Gy shows some effect of saturation, thereby slightly diminishing the ability to quantify higher exposures. Analyses of these gene transcripts may be advantageous for use in a field-portable device designed to assess exposures in mass casualty situations or in clinical radiation emergencies.« less
Authors:
 [1] ;  [2] ; ; ;  [1] ; ;  [3] ;  [4] ;  [3]
  1. Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States)
  2. Department of Radiation Oncology, Wayne State University, Detroit, Michigan (United States)
  3. Department of Electrical and Computer Engineering, Wayne State University, Detroit, Michigan (United States)
  4. Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan (United States)
Publication Date:
OSTI Identifier:
22416505
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 88; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BLOOD; COBALT 60; COMPARATIVE EVALUATIONS; DOSIMETRY; GAMMA RADIATION; GENES; HUMAN POPULATIONS; MESSENGER-RNA; POLYMERASE CHAIN REACTION; RADIATION DOSES; SENSITIVITY; SPECIFICITY; STATISTICAL MODELS