National security concerns regarding radiological incidents, accidental or intentional in nature, have increased substantially over the past few years. A primary area of intense planning is the assessment of exposed individuals and timely medical management. However, exposed individuals who receive survivable radiation doses may develop delayed effects of acute radiation exposure many months or years later. Therefore, it is necessary to identify such individuals and determine whether their symptoms may have been initiated by radiation and require complex medical interventions. We previously developed early response metabolomic biosignatures in biofluids from non-human primates exposed to a total body gamma radiation dose of 4 Gy (up to 60 days). A follow-up of these animals has been ongoing with samples consistently collected every few months for up to 2 years after exposure, providing a unique cohort to determine if a radiation signal persists longer than 2 months. Metabolic fingerprinting in urine and serum determined that exposed animals remain metabolically different from pre-exposure levels and from age-matched controls, and the pre-determined biosignature maintains high sensitivity and specificity. Significant perturbations in tricarboxylic acid intermediates, cofactors and nucleotide metabolism were noted, signifying energetic changes that could be attributed to or perpetuate altered mitochondrial dynamics. Importantly, these animals have begun developing diseases such as hypertension much earlier than their age-matched controls, further emphasizing that radiation exposure may lead to accelerated aging. This NHP cohort provides important information and highlights the potential of metabolomics in determining persistent changes and a radiation-specific signature that can be correlated to phenotype.
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Research Article|
November 07 2024
Long-term Radiation Signal Persistence in Urine and Blood: A Two-year Analysis in Non-human Primates Exposed to a 4 Gy Total-Body Gamma-Radiation Dose
Emma Kosowski;
Emma Kosowski
aDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
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John D. Olson;
John D. Olson
bDepartment of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Jean Gardin;
Jean Gardin
bDepartment of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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George W. Schaaf;
George W. Schaaf
bDepartment of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Denise Nishita;
Denise Nishita
cSRI International, BioSciences Division, Menlo Park, California
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Simon Authier;
Simon Authier
dCharles River Laboratories, Laval, Quebec, Canada
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Polly Chang;
Polly Chang
cSRI International, BioSciences Division, Menlo Park, California
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David J. Brenner;
David J. Brenner
eCenter for Radiological Research, Columbia University Irving Medical Center, New York, New York
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Albert J. Fornace, Jr.;
Albert J. Fornace, Jr.
aDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
fDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
gCenter for Metabolomic Studies, Georgetown University
hDepartment of Radiation Medicine, Georgetown University, Washington, DC
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J. Mark Cline;
J. Mark Cline
bDepartment of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Evagelia C. Laiakis
Evagelia C. Laiakis
1
aDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
fDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
gCenter for Metabolomic Studies, Georgetown University
hDepartment of Radiation Medicine, Georgetown University, Washington, DC
1Corresponding author’s address: Evagelia C. Laiakis, Ph.D., Georgetown University, 3970 Reservoir Rd, NW, New Research Building, Room EP11, Washington, DC 20057; email: [email protected].
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Radiat Res (2024)
Article history
Received:
December 21 2023
Accepted:
July 08 2024
Citation
Emma Kosowski, John D. Olson, Jean Gardin, George W. Schaaf, Denise Nishita, Simon Authier, Polly Chang, David J. Brenner, Albert J. Fornace, J. Mark Cline, Evagelia C. Laiakis; Long-term Radiation Signal Persistence in Urine and Blood: A Two-year Analysis in Non-human Primates Exposed to a 4 Gy Total-Body Gamma-Radiation Dose. Radiat Res 2024; doi: https://doi.org/10.1667/RADE-23-00261.1
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