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

• Published in: International journal of radiation oncology, biology, physics Vol. 88; no. 4; pp. 933 - 939
• Main Authors: Tucker, James D., PhD, Joiner, Michael C., PhD, Thomas, Robert A., PhD, Grever, William E., PhD, Bakhmutsky, Marina V., PhD, Chinkhota, Chantelle N., PhD, Smolinski, Joseph M., PhD, Divine, George W., PhD, Auner, Gregory W., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2014
• Subjects: Adult; Ataxia Telangiectasia Mutated Proteins - genetics; BLOOD; Blood - radiation effects; COBALT 60; Cobalt Radioisotopes; COMPARATIVE EVALUATIONS; Cyclin-Dependent Kinase Inhibitor p21 - genetics; DOSIMETRY; GAMMA RADIATION; Gene Expression; Gene Expression Profiling - methods; GENES; Genetic Markers; Glycoproteins - genetics; Growth Differentiation Factor 15 - genetics; Hematology, Oncology and Palliative Medicine; HUMAN POPULATIONS; Humans; MESSENGER-RNA; Nerve Tissue Proteins - genetics; POLYMERASE CHAIN REACTION; Radiation Dosage; RADIATION DOSES; Radiation Injuries - genetics; Radioactive Fallout - adverse effects; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; Radiometry - methods; Real-Time Polymerase Chain Reaction - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - analysis; SENSITIVITY; Sensitivity and Specificity; SPECIFICITY; STATISTICAL MODELS
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2013.11.248

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 (R2 ). 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 predicted 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.