A translatable predictor of human radiation exposure. PLoS One 2014;9(9):e107897
Date
09/26/2014Pubmed ID
25255453Pubmed Central ID
PMC4177872DOI
10.1371/journal.pone.0107897Scopus ID
2-s2.0-84907588604 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
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.
Author List
Lucas J, Dressman HK, Suchindran S, Nakamura M, Chao NJ, Himburg H, Minor K, Phillips G, Ross J, Abedi M, Terbrueggen R, Chute JPAuthor
Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Animals
Blood Cells
Environmental Exposure
Female
Humans
Male
Mice
Middle Aged
Radiation Dosage
Radiation Injuries
Radiometry
Transcriptome
Whole-Body Irradiation
Young Adult
