دورية أكاديمية
Age-Dependent Differences in Radiation-Induced DNA Damage Responses in Intestinal Stem Cells.
| العنوان: | Age-Dependent Differences in Radiation-Induced DNA Damage Responses in Intestinal Stem Cells. |
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| المؤلفون: | Zhou G; Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 754-8553, Japan., Shimura T; Department of Environmental Health, National Institute of Public Health, Saitama 351-0197, Japan., Yoneima T; School of Medicine, Hiroshima University, Hiroshima 754-8551, Japan., Nagamachi A; Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 754-8553, Japan., Kanai A; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan., Doi K; Department of Radiation Regulatory Science Research, Institute for Radiological Sciences, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Sasatani M; Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 754-8553, Japan. |
| المصدر: | International journal of molecular sciences [Int J Mol Sci] 2024 Sep 23; Vol. 25 (18). Date of Electronic Publication: 2024 Sep 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
| مواضيع طبية MeSH: | DNA Damage*/radiation effects , Stem Cells*/radiation effects , Stem Cells*/metabolism , Stem Cells*/cytology, Animals ; Mice ; Receptors, G-Protein-Coupled/metabolism ; Receptors, G-Protein-Coupled/genetics ; Apoptosis/radiation effects ; Intestinal Mucosa/radiation effects ; Intestinal Mucosa/metabolism ; Intestines/radiation effects ; Intestines/pathology ; DNA Repair ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Protein p53/genetics ; Age Factors ; Adult Stem Cells/radiation effects ; Adult Stem Cells/metabolism ; Mice, Inbred C57BL |
| مستخلص: | Age at exposure is a critical modifier of the risk of radiation-induced cancer. However, the effects of age on radiation-induced carcinogenesis remain poorly understood. In this study, we focused on tissue stem cells using Lgr5-eGFP-ires-Cre ERT2 mice to compare radiation-induced DNA damage responses between Lgr5+ and Lgr5- intestinal stem cells. Three-dimensional immunostaining analyses demonstrated that radiation induced apoptosis and the mitotic index more efficiently in adult Lgr5- stem cells than in adult Lgr5+ stem cells but not in infants, regardless of Lgr5 expression. Supporting this evidence, rapid and transient p53 activation occurred after irradiation in adult intestinal crypts but not in infants. RNA sequencing revealed greater variability in gene expression in adult Lgr5+ stem cells than in infant Lgr5+ stem cells after irradiation. Notably, the cell cycle and DNA repair pathways were more enriched in adult stem cells than in infant stem cells after irradiation. Our findings suggest that radiation-induced DNA damage responses in mouse intestinal crypts differ between infants and adults, potentially contributing to the age-dependent susceptibility to radiation carcinogenesis. |
| معلومات مُعتمدة: | none Research project on the Health Effects of Radiation organized by Ministry of the Environment, Japan.; 23K25008 Japan Society for the Promotion of Science, JSPS KAKENHI; 22H03754 Japan Society for the Promotion of Science, JSPS KAKENHI; 23K28232 Japan Society for the Promotion of Science, JSPS KAKENHI; 23H03542 Japan Society for the Promotion of Science, JSPS KAKENHI; 20K21846 Japan Society for the Promotion of Science, JSPS KAKENHI; NIFS20KOCA004 National Institute for Fusion Science Collaborative Research Program; NIFS23HDCF005 National Institute for Fusion Science Collaborative Research Program; none QST Research Collaboration; none the Program of the Network-Type Joint Usage/Research Center for Radiation Disaster Medical Science at Hiroshima University, Nagasaki University, and Fukushima Medical University.; none Initiative for Realizing Diversity in the Research Environment (Specific Correspondence Type), a support project for the Development of Human Resources in Science and Technology conducted by the Ministry of Education, Culture, Sports, Science and Technolo; NIFS17KOCA002 National Institute for Fusion Science Collaborative Research Program |
| فهرسة مساهمة: | Keywords: DNA damage response; DNA repair; Lgr5+ intestinal stem cells; age at exposure; apoptosis; cell cycle; gene expression variability; intestinal crypts; p53 activation; radiation; stem cell |
| المشرفين على المادة: | 0 (Lgr5 protein, mouse) 0 (Receptors, G-Protein-Coupled) 0 (Tumor Suppressor Protein p53) |
| تواريخ الأحداث: | Date Created: 20240928 Date Completed: 20240928 Latest Revision: 20240928 |
| رمز التحديث: | 20240929 |
| DOI: | 10.3390/ijms251810213 |
| PMID: | 39337697 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1422-0067 |
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| DOI: | 10.3390/ijms251810213 |