Radiation Signature in Plasma Metabolome of Total-Body Irradiated Nonhuman Primates and Clinical Patients
Abstract
:1. Introduction
2. Results
2.1. Metabolite Alterations in Plasma from TBI Leukemia Patients as Indicators of Radiation Exposure
2.2. Metabolite Alterations in NHP Plasma as Indicators of Radiation Exposure
3. Discussion
4. Materials and Methods
4.1. Experimental Design
4.2. Patient Study
4.2.1. Leukemia Patients
4.2.2. Irradiation of Patients
4.2.3. Blood Collection and Plasma Separation
4.3. NHP Study
4.3.1. Animals and Animal Care
4.3.2. Irradiation of NHPs
4.3.3. Blood Collection from NHPs and Plasma Separation
4.4. Metabolite Extraction and LC-MS Analysis
4.5. Data Processing and Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Human Pathways | Total | Expected | Hits | p-Value | FDR |
Steroidogenesis | 43 | 0.17 | 2 | 0.010 | 0.051 |
Porphyrin metabolism | 40 | 0.16 | 1 | 0.151 | 0.755 |
Steroid biosynthesis | 48 | 0.19 | 1 | 0.179 | 0.895 |
Bile acid biosynthesis | 65 | 0.26 | 1 | 0.236 | 1.000 |
Tyrosine metabolism | 70 | 0.28 | 1 | 0.252 | 1.000 |
NHP Pathways | Total | Expected | Hits | p-Value | FDR |
Steroid hormone biosynthesis | 87 | 0.39 | 3 | 0.005 | 0.030 |
Porphyrin metabolism | 31 | 0.14 | 2 | 0.007 | 0.045 |
Citrate cycle (TCA cycle) | 20 | 0.09 | 1 | 0.086 | 0.517 |
Pyruvate metabolism | 23 | 0.10 | 1 | 0.099 | 0.591 |
Glyoxylate and dicarboxylate metabolism | 32 | 0.14 | 1 | 0.135 | 0.810 |
Arachidonic acid metabolism | 45 | 0.20 | 1 | 0.185 | 1.000 |
Human Pathways | Overlap Size | Pathway Size |
---|---|---|
C21-steroid hormone biosynthesis and metabolism | 4 | 26 |
Glycosphingolipid metabolism | 1 | 4 |
Tyrosine metabolism | 1 | 6 |
NHP pathways | ||
C21-steroid hormone biosynthesis and metabolism | 10 | 35 |
Glycerophospholipid metabolism | 9 | 29 |
Prostaglandin formation from arachidonate | 5 | 6 |
Ascorbate (vitamin C) and aldarate metabolism | 4 | 6 |
Porphyrin metabolism | 4 | 8 |
TCA cycle | 3 | 4 |
Leukotriene metabolism | 3 | 6 |
Glycolysis and gluconeogenesis | 2 | 2 |
Omega-6 fatty acid metabolism | 2 | 3 |
Glycosylphosphatidylinositol-anchor biosynthesis | 2 | 3 |
Drug metabolism—cytochrome P450 | 2 | 3 |
Putative anti-inflammatory metabolites formation from EPA | 2 | 3 |
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Tichy, A.; Carpenter, A.D.; Li, Y.; Rydlova, G.; Rehulka, P.; Markova, M.; Milanova, M.; Chmil, V.; Cheema, A.K.; Singh, V.K. Radiation Signature in Plasma Metabolome of Total-Body Irradiated Nonhuman Primates and Clinical Patients. Int. J. Mol. Sci. 2024, 25, 9208. https://doi.org/10.3390/ijms25179208
Tichy A, Carpenter AD, Li Y, Rydlova G, Rehulka P, Markova M, Milanova M, Chmil V, Cheema AK, Singh VK. Radiation Signature in Plasma Metabolome of Total-Body Irradiated Nonhuman Primates and Clinical Patients. International Journal of Molecular Sciences. 2024; 25(17):9208. https://doi.org/10.3390/ijms25179208
Chicago/Turabian StyleTichy, Ales, Alana D. Carpenter, Yaoxiang Li, Gabriela Rydlova, Pavel Rehulka, Marketa Markova, Marcela Milanova, Vojtech Chmil, Amrita K. Cheema, and Vijay K. Singh. 2024. "Radiation Signature in Plasma Metabolome of Total-Body Irradiated Nonhuman Primates and Clinical Patients" International Journal of Molecular Sciences 25, no. 17: 9208. https://doi.org/10.3390/ijms25179208