Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model
Countermeasures for radiation diagnosis, prognosis, and treatment are trailing behind the proliferation of nuclear energy and weaponry. Radiation injury mechanisms at the systems biology level are not fully understood. Here, mice skin biopsies at h2, d4, d7, d21, and d28 after exposure to 1, 3, 6, o...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/8/254 |
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| author | Abdulnaser Alkhalil John Clifford Stacyann M. Miller Aarti Gautam Marti Jett Rasha Hammamieh Lauren T. Moffatt Jeffrey W. Shupp |
| author_facet | Abdulnaser Alkhalil John Clifford Stacyann M. Miller Aarti Gautam Marti Jett Rasha Hammamieh Lauren T. Moffatt Jeffrey W. Shupp |
| author_sort | Abdulnaser Alkhalil |
| collection | DOAJ |
| description | Countermeasures for radiation diagnosis, prognosis, and treatment are trailing behind the proliferation of nuclear energy and weaponry. Radiation injury mechanisms at the systems biology level are not fully understood. Here, mice skin biopsies at h2, d4, d7, d21, and d28 after exposure to 1, 3, 6, or 20 Gy whole-body ionizing radiation were evaluated for the potential application of transcriptional alterations in radiation diagnosis and prognosis. Exposure to 20 Gy was lethal by d7, while mice who received 1, 3, or 6 Gy survived the 28-day time course. A Sammon plot separated samples based on survival and time points (TPs) within lethal (20 Gy) and sublethal doses. The differences in the numbers, regulation mode, and fold change of significantly differentially transcribed genes (SDTGs, <i>p</i> < 0.05 and FC > 2) were identified between lethal and sublethal doses, and down and upregulation dominated transcriptomes during the first post-exposure week, respectively. The numbers of SDTGs and the percentages of upregulated ones revealed stationary downregulation post-lethal dose in contrast to responses to sublethal doses which were dynamic and largely upregulated. Longitudinal up/downregulated SDTGs ratios suggested delayed and extended responses with increasing IR doses in the sublethal range and lethal-like responses in late TPs. This was supported by the distributions of common and unique genes across TPs within each dose. Several genes with potential dosimetric marker applications were identified. Immune, fibrosis, detoxification, hematological, neurological, gastric, cell survival, migration, and proliferation radiation response pathways were identified, with the majority predicted to be activated after sublethal and inactivated after lethal exposures, particularly during the first post-exposure week. |
| first_indexed | 2024-03-09T13:37:56Z |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-09T13:37:56Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-3291aab9eaaf441bb4b63b532874e3be2023-11-30T21:09:26ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-08-014483711373410.3390/cimb44080254Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse ModelAbdulnaser Alkhalil0John Clifford1Stacyann M. Miller2Aarti Gautam3Marti Jett4Rasha Hammamieh5Lauren T. Moffatt6Jeffrey W. Shupp7Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USAPain and Sensory Trauma Care Research Team, US Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX 78234, USAMedical Readiness Systems Biology Branch, Center for Military Psychiatry and Neuroscience Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAMedical Readiness Systems Biology Branch, Center for Military Psychiatry and Neuroscience Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAMedical Readiness Systems Biology Branch, Center for Military Psychiatry and Neuroscience Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAMedical Readiness Systems Biology Branch, Center for Military Psychiatry and Neuroscience Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAFirefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USAFirefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USACountermeasures for radiation diagnosis, prognosis, and treatment are trailing behind the proliferation of nuclear energy and weaponry. Radiation injury mechanisms at the systems biology level are not fully understood. Here, mice skin biopsies at h2, d4, d7, d21, and d28 after exposure to 1, 3, 6, or 20 Gy whole-body ionizing radiation were evaluated for the potential application of transcriptional alterations in radiation diagnosis and prognosis. Exposure to 20 Gy was lethal by d7, while mice who received 1, 3, or 6 Gy survived the 28-day time course. A Sammon plot separated samples based on survival and time points (TPs) within lethal (20 Gy) and sublethal doses. The differences in the numbers, regulation mode, and fold change of significantly differentially transcribed genes (SDTGs, <i>p</i> < 0.05 and FC > 2) were identified between lethal and sublethal doses, and down and upregulation dominated transcriptomes during the first post-exposure week, respectively. The numbers of SDTGs and the percentages of upregulated ones revealed stationary downregulation post-lethal dose in contrast to responses to sublethal doses which were dynamic and largely upregulated. Longitudinal up/downregulated SDTGs ratios suggested delayed and extended responses with increasing IR doses in the sublethal range and lethal-like responses in late TPs. This was supported by the distributions of common and unique genes across TPs within each dose. Several genes with potential dosimetric marker applications were identified. Immune, fibrosis, detoxification, hematological, neurological, gastric, cell survival, migration, and proliferation radiation response pathways were identified, with the majority predicted to be activated after sublethal and inactivated after lethal exposures, particularly during the first post-exposure week.https://www.mdpi.com/1467-3045/44/8/254radiationtranscriptomesskinmice |
| spellingShingle | Abdulnaser Alkhalil John Clifford Stacyann M. Miller Aarti Gautam Marti Jett Rasha Hammamieh Lauren T. Moffatt Jeffrey W. Shupp Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model Current Issues in Molecular Biology radiation transcriptomes skin mice |
| title | Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model |
| title_full | Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model |
| title_fullStr | Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model |
| title_full_unstemmed | Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model |
| title_short | Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model |
| title_sort | transcriptomes of wet skin biopsies predict outcomes after ionizing radiation exposure with potential dosimetric applications in a mouse model |
| topic | radiation transcriptomes skin mice |
| url | https://www.mdpi.com/1467-3045/44/8/254 |
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