A translatable predictor of human radiation exposure.

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

Cordes, Nils

United States

2015-12-03T15:18:43Z

2014

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.

http://www.ncbi.nlm.nih.gov/pubmed/25255453

PONE-D-14-09904

1932-6203

https://hdl.handle.net/10161/10977

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0107897

Adult

Aged

Animals

Blood Cells

Environmental Exposure

Female

Humans

Male

Mice

Middle Aged

Radiation Dosage

Radiation Injuries

Radiometry

Transcriptome

Translational Medical Research

Whole-Body Irradiation

Young Adult

A translatable predictor of human radiation exposure.

Journal article

Chao, Nelson J|0000-0001-6725-7220

http://www.ncbi.nlm.nih.gov/pubmed/25255453

e107897

9

Basic Science Departments

Biostatistics & Bioinformatics

Clinical Science Departments

Duke

Duke Cancer Institute

Global Health Institute

Immunology

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cellular Therapy

Molecular Genetics and Microbiology

Pathology

School of Medicine

Social Science Research Institute

University Institutes and Centers

Published online

9