In the event of a mass casualty radiation scenario, rapid assessment of patients' health and triage is required for optimal resource utilization. Identifying the level and extent of exposure as well as prioritization of care is extremely challenging under such disaster conditions. Blood-based biomarkers, such as RNA integrity numbers (RIN), could help healthcare personnel quickly and efficiently determine the extent and effect of multiple injuries on patients' health. Evaluation of the effect of different radiation doses, alone or in combination with burn injury, on total RNA integrity over multiple time points was performed. Total RNA integrity was tallied in blood samples for potential application as a marker of radiation exposure and survival. Groups of aged mice (3–6 mice/group, 13–18 months old) received 0.5, 1, 5, 10 or 20 Gy ionizing radiation. Two additional mouse groups received low-dose irradiation (0.5 or 1 Gy) with a 15% total body surface area (TBSA) burn injury. Animals were euthanized at 2 or 12 h and at day 1, 2, 3, 7 or 14 postirradiation, or when injury-mediated mortality occurred. Total RNA was isolated from blood. The quality of RNA was evaluated and RNA RIN were obtained. Analysis of RIN indicated that blood showed the clearest radiation effect. There was a time- and radiation-dose-dependent reduction in RIN that was first detectable at 12 h postirradiation for all doses in animals receiving irradiation alone. This effect was reversible in lower-dose groups (i.e., 0.5, 1 and 5 Gy) that survived to the end of the study (14 days). In contrast, the effect persisted for 10 and 20 Gy groups, which showed suppression of RIN values <4.5 with high mortalities. Radiation doses of 20 Gy were lethal and required euthanasia by day 6. A low RIN (<2.5) at any time point was associated with 100% mortality. Combined radiation-burn injury produced significantly increased mortality such that no dually-injured animals survived beyond day 3, and no radiation dose >1 Gy resulted in survival past day 1. More modest suppression of RIN was observed in the surviving dually challenged mice, and no statistically significant changes were identified in RIN values of burn-only mice at any time point. In this study of an animal model, a proof of concept is presented for a simple and accurate method of assessing radiation dose exposure in blood which potentially predicts lethality. RIN assessment of blood-derived RNA could form the basis for a clinical decision-support tool to guide healthcare providers under the strenuous conditions of a radiation-based mass casualty event.
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June 2020
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April 13 2020
Blood RNA Integrity is a Direct and Simple Reporter of Radiation Exposure and Prognosis: A Pilot Study
Abdulnaser Alkhalil;
Abdulnaser Alkhalil
1
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010
1 Address for correspondence: Firefighters' Burn and Surgical Research Laboratory, George Hyman Research Building, MedStar Washington Hospital Center, Room 306, 108 Irving St., NW, Washington, DC 20010-2975; email: [email protected].
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John. L. Clifford;
John. L. Clifford
Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702
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Robert Ball;
Robert Ball
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010
The Burn Center, MedStar Washington Hospital Center, Washington, DC 20010
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Anna Day;
Anna Day
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010
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Rosanna Chan;
Rosanna Chan
Department of Radiology, MedStar Washington Hospital Center, Washington, DC 20010
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Bonnie C. Carney;
Bonnie C. Carney
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, DC 20010
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Stacy Ann Miller;
Stacy Ann Miller
Integrative Systems Biology, The Oak Ridge Institute for Science and Education, Fort Detrick, Maryland 21702-5000
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Ross Campbell;
Ross Campbell
Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702
Advanced Biomedical Computational Science, Frederick National Lab for Cancer Research/Advanced Biomedical Computational, Frederick, Maryland, 21702
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Raina Kumar;
Raina Kumar
Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702
Advanced Biomedical Computational Science, Frederick National Lab for Cancer Research/Advanced Biomedical Computational, Frederick, Maryland, 21702
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Aarti Gautam;
Aarti Gautam
Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702
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Rasha Hammamieh;
Rasha Hammamieh
Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702
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Lauren T. Moffatt;
Lauren T. Moffatt
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, DC 20010
Department of Surgery, Georgetown University School of Medicine, Washington, DC 20010
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Jeffrey W. Shupp
Jeffrey W. Shupp
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010
The Burn Center, MedStar Washington Hospital Center, Washington, DC 20010
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, DC 20010
Department of Surgery, Georgetown University School of Medicine, Washington, DC 20010
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Radiat Res (2020) 193 (6): 543–551.
Article history
Received:
September 24 2019
Accepted:
March 09 2020
Citation
Abdulnaser Alkhalil, John. L. Clifford, Robert Ball, Anna Day, Rosanna Chan, Bonnie C. Carney, Stacy Ann Miller, Ross Campbell, Raina Kumar, Aarti Gautam, Rasha Hammamieh, Lauren T. Moffatt, Jeffrey W. Shupp; Blood RNA Integrity is a Direct and Simple Reporter of Radiation Exposure and Prognosis: A Pilot Study. Radiat Res 1 June 2020; 193 (6): 543–551. doi: https://doi.org/10.1667/RR15527.1
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