Abstract

Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy) with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.

Highlights

  • In today’s society, there is a distinct threat of terrorist attacks from chemical, biological, radiological, and/or nuclear weapons

  • Populations that are exposed to high radiation doses develop acute radiation syndrome (ARS), an acute illness caused by whole body exposure to a high dose of penetrating radiation over a short interval

  • In the time-dependent analysis the number of proteins uniquely identified in the plasma samples was greatest at day 7 (68 proteins) with 6.7 Gy radiation exposure as compared with the higher dose of radiation in which the majority of uniquely identified proteins were identified on day 4 (75 proteins) (Fig 1B)

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Summary

Introduction

In today’s society, there is a distinct threat of terrorist attacks from chemical, biological, radiological, and/or nuclear weapons. Populations that are exposed to high radiation doses develop acute radiation syndrome (ARS), an acute illness caused by whole body exposure to a high dose of penetrating radiation over a short interval. Exposure to high ionizing radiation levels is associated with a wide range of biological effects including damage to macromolecules (e.g., DNA, proteins and lipids), increased mitochondria-dependent generation of reactive oxygen species (ROS), apoptosis, stress-related responses, and defects in the ability of cells to divide. Dose dependent changes in the plasma proteome after total body irradiation of non-human primates default.aspx): R01GM106024 (AT), P20GM103429 (N/A), and P20GM109005 (MHJ); National Cancer Institute (https://www.cancer.gov/): R33CA173264 (AT); National Institute of Environmental Health Sciences (http://www.niehs.nih.gov/): R21ES025268 (AT) and the National Center for Advancing Translational Sciences The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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