Gene expression-based dosimetry by dose and time in mice following acute radiation exposure.

Autor: James D Tucker, George W Divine, William E Grever, Robert A Thomas, Michael C Joiner, Joseph M Smolinski, Gregory W Auner
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS ONE, Vol 8, Iss 12, p e83390 (2013)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0083390
Popis: 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.
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