دورية أكاديمية
أعرض في EDS

Impact of GADD45A on Radiation Biodosimetry Using Mouse Peripheral Blood.

التفاصيل البيبلوغرافية
العنوان: Impact of GADD45A on Radiation Biodosimetry Using Mouse Peripheral Blood.
المؤلفون: Broustas CG; Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York 10032., Mukherjee S; Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York 10032., Shuryak I; Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York 10032., Taraboletti A; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057., Angdisen J; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057., Ake P; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057., Fornace AJ; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057.; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057., Amundson SA; Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York 10032.
المصدر: Radiation research [Radiat Res] 2023 Sep 01; Vol. 200 (3), pp. 296-306.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Radiation Research Society Country of Publication: United States NLM ID: 0401245 Publication Model: Print Cited Medium: Internet ISSN: 1938-5404 (Electronic) Linking ISSN: 00337587 NLM ISO Abbreviation: Radiat Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Bozeman, MT : Radiation Research Society
Original Publication: Charlottesville, VA : Kluge Carden Jennnings Pub. Co.
مواضيع طبية MeSH: Cell Cycle Proteins*/genetics , Cell Cycle Proteins*/metabolism , Inflammation*/genetics, Animals ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; X-Rays
مستخلص: High-dose-radiation exposure in a short period of time leads to radiation syndromes characterized by severe acute and delayed organ-specific injury accompanied by elevated organismal morbidity and mortality. Radiation biodosimetry based on gene expression analysis of peripheral blood is a valuable tool to detect exposure to radiation after a radiological/nuclear incident and obtain useful biological information that could predict tissue and organismal injury. However, confounding factors, including chronic inflammation, can potentially obscure the predictive power of the method. GADD45A (Growth arrest and DNA damage-inducible gene a) plays important roles in cell growth control, differentiation, DNA repair, and apoptosis. GADD45A-deficient mice develop an autoimmune disease, similar to human systemic lupus erythematosus, characterized by severe hematological disorders, kidney disease, and premature death. The goal of this study was to elucidate how pre-existing inflammation in mice, induced by GADD45A ablation, can affect radiation biodosimetry. We exposed wild-type and GADD45A knockout male C57BL/6J mice to 7 Gy of X rays and 24 h later RNA was isolated from whole blood and subjected to whole genome microarray and gene ontology analyses. Dose reconstruction analysis using a gene signature trained on gene expression data from irradiated wild-type male mice showed accurate reconstruction of either a 0 Gy or 7 Gy dose with root mean square error of ± 1.05 Gy (R^2 = 1.00) in GADD45A knockout mice. Gene ontology analysis revealed that irradiation of both wild-type and GADD45A-null mice led to a significant overrepresentation of pathways associated with morbidity and mortality, as well as organismal cell death. However, based on their z-score, these pathways were predicted to be more significantly overrepresented in GADD45A-null mice, implying that GADD45A deletion may exacerbate the deleterious effects of radiation on blood cells. Numerous immune cell functions and quantities were predicted to be underrepresented in both genotypes; however, differentially expressed genes from irradiated GADD45A knockout mice predicted an increased deterioration in the numbers of T lymphocytes, as well as myeloid cells, compared with wild-type mice. Furthermore, an overrepresentation of genes associated with radiation-induced hematological malignancies was associated with GADD45A knockout mice, whereas hematopoietic and progenitor cell functions were predicted to be downregulated in irradiated GADD45A knockout mice. In conclusion, despite the significant differences in gene expression between wild-type and GADD45A knockout mice, it is still feasible to identify a panel of genes that could accurately distinguish between irradiated and control mice, irrespective of pre-existing inflammation status.
(©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)
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معلومات مُعتمدة: U19 AI067773 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (GADD45A protein, human)
0 (Gadd45a protein, mouse)
تواريخ الأحداث: Date Created: 20230708 Date Completed: 20230928 Latest Revision: 20231010
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10559452
DOI: 10.1667/RADE-23-00052.1
PMID: 37421415
قاعدة البيانات: MEDLINE
الوصف
تدمد:1938-5404
DOI:10.1667/RADE-23-00052.1