Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation
Abstract The risk of exposure of the general public or military personnel to high levels of ionizing radiation from nuclear weapons or radiological accidents is a dire national security matter. The development of advanced molecular biodosimetry methods, those that measure biological response, such a...
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| Format: | Article |
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BMC
2023-05-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-023-09385-3 |
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| author | Neetha Nanoth Vellichirammal Sahil Sethi Nagavardhini Avuthu Stephen Y. Wise Alana D. Carpenter Oluseyi O. Fatanmi Chittibabu Guda Vijay K. Singh |
| author_facet | Neetha Nanoth Vellichirammal Sahil Sethi Nagavardhini Avuthu Stephen Y. Wise Alana D. Carpenter Oluseyi O. Fatanmi Chittibabu Guda Vijay K. Singh |
| author_sort | Neetha Nanoth Vellichirammal |
| collection | DOAJ |
| description | Abstract The risk of exposure of the general public or military personnel to high levels of ionizing radiation from nuclear weapons or radiological accidents is a dire national security matter. The development of advanced molecular biodosimetry methods, those that measure biological response, such as transcriptomics, to screen large populations of radiation-exposed victims is key to improving survival outcomes during radiological mass casualty scenarios. In this study, nonhuman primates were exposed to either 12.0 Gy cobalt-60 gamma (total-body irradiation, TBI) or X-ray (partial-body irradiation, PBI) 24 h after administration of a potential radiation medical countermeasure, gamma-tocotrienol (GT3). Changes in the jejunal transcriptomic profiles in GT3-treated and irradiated animals were compared to healthy controls to assess the extent of radiation damage. No major effect of GT3 on radiation-induced transcriptome at this radiation dose was identified. About 80% of the pathways with a known activation or repression state were commonly observed between both exposures. Several common pathways activated due to irradiation include FAK signaling, CREB signaling in the neurons, phagosome formation, and G-protein coupled signaling pathway. Sex-specific differences associated with excessive mortality among irradiated females were identified in this study, including Estrogen receptor signaling. Differential pathway activation was also identified across PBI and TBI, pointing towards altered molecular response for different degrees of bone marrow sparing and radiation doses. This study provides insight into radiation-induced changes in jejunal transcriptional profiles, supporting the investigation for the identification of biomarkers for radiation injury and countermeasure efficacy. |
| first_indexed | 2024-03-13T09:03:49Z |
| format | Article |
| id | doaj.art-99c4a7b85d414c0bbcf85c39bfb8bbfe |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-13T09:03:49Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-99c4a7b85d414c0bbcf85c39bfb8bbfe2023-05-28T11:09:18ZengBMCBMC Genomics1471-21642023-05-0124111310.1186/s12864-023-09385-3Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiationNeetha Nanoth Vellichirammal0Sahil Sethi1Nagavardhini Avuthu2Stephen Y. Wise3Alana D. Carpenter4Oluseyi O. Fatanmi5Chittibabu Guda6Vijay K. Singh7Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical CenterDepartment of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical CenterDepartment of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical CenterDivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health SciencesDivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health SciencesDivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health SciencesDepartment of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical CenterDivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health SciencesAbstract The risk of exposure of the general public or military personnel to high levels of ionizing radiation from nuclear weapons or radiological accidents is a dire national security matter. The development of advanced molecular biodosimetry methods, those that measure biological response, such as transcriptomics, to screen large populations of radiation-exposed victims is key to improving survival outcomes during radiological mass casualty scenarios. In this study, nonhuman primates were exposed to either 12.0 Gy cobalt-60 gamma (total-body irradiation, TBI) or X-ray (partial-body irradiation, PBI) 24 h after administration of a potential radiation medical countermeasure, gamma-tocotrienol (GT3). Changes in the jejunal transcriptomic profiles in GT3-treated and irradiated animals were compared to healthy controls to assess the extent of radiation damage. No major effect of GT3 on radiation-induced transcriptome at this radiation dose was identified. About 80% of the pathways with a known activation or repression state were commonly observed between both exposures. Several common pathways activated due to irradiation include FAK signaling, CREB signaling in the neurons, phagosome formation, and G-protein coupled signaling pathway. Sex-specific differences associated with excessive mortality among irradiated females were identified in this study, including Estrogen receptor signaling. Differential pathway activation was also identified across PBI and TBI, pointing towards altered molecular response for different degrees of bone marrow sparing and radiation doses. This study provides insight into radiation-induced changes in jejunal transcriptional profiles, supporting the investigation for the identification of biomarkers for radiation injury and countermeasure efficacy.https://doi.org/10.1186/s12864-023-09385-3Gamma tocotrienolJejunum, Nonhuman primatesRadiation injuryRadiation countermeasureTranscriptomics, Total-body irradiation, Partial-body irradiation |
| spellingShingle | Neetha Nanoth Vellichirammal Sahil Sethi Nagavardhini Avuthu Stephen Y. Wise Alana D. Carpenter Oluseyi O. Fatanmi Chittibabu Guda Vijay K. Singh Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation BMC Genomics Gamma tocotrienol Jejunum, Nonhuman primates Radiation injury Radiation countermeasure Transcriptomics, Total-body irradiation, Partial-body irradiation |
| title | Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation |
| title_full | Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation |
| title_fullStr | Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation |
| title_full_unstemmed | Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation |
| title_short | Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation |
| title_sort | transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total or partial body radiation |
| topic | Gamma tocotrienol Jejunum, Nonhuman primates Radiation injury Radiation countermeasure Transcriptomics, Total-body irradiation, Partial-body irradiation |
| url | https://doi.org/10.1186/s12864-023-09385-3 |
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