A Translatable Predictor of Human Radiation Exposure

• Published in: PloS one Vol. 9; no. 9; p. e107897
• Main Authors: Lucas, Joseph, Dressman, Holly K., Suchindran, Sunil, Nakamura, Mai, Chao, Nelson J., Himburg, Heather, Minor, Kerry, Phillips, Gary, Ross, Joel, Abedi, Majid, Terbrueggen, Robert, Chute, John P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.09.2014; Public Library of Science (PLoS)
• Subjects: Accuracy; Adult; Aged; Algorithms; Animals; Assaying; Biology and Life Sciences; Blood; Blood Cells - metabolism; Blood Cells - radiation effects; Bombs; Cell cycle; Chemotherapy; Classifiers; Computer and Information Sciences; Diagnosis; Drug dosages; Environmental Exposure - analysis; Exposure; Female; Gene expression; Genomes; Health care; Health risks; Humans; Immunology; Ionizing radiation; Irradiated; Irradiation; Kinases; Male; Medicine; Medicine and Health Sciences; Mice; Middle Aged; Multivariate analysis; Nuclear accidents; Nuclear devices; Patients; Peripheral blood; Public health; Radiation; Radiation Dosage; Radiation effects; Radiation exposure; Radiation injuries; Radiation Injuries - blood; Radiation Injuries - genetics; Radiation therapy; Radiometry; Research and Analysis Methods; Samplers; Security; Signatures; Terrorism; Transcriptome - radiation effects; Translation (Genetics); Translational Medical Research - methods; Whole-Body Irradiation - adverse effects; Young Adult; Los Angeles California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107897

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.