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Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma
https://repo.qst.go.jp/records/85043
https://repo.qst.go.jp/records/85043671a3b38-e8af-4122-b34f-26d8ffe247e7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-02-28 | |||||
| タイトル | ||||||
| タイトル | Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Akira, Fujimori
× Akira, Fujimori× Hirokazu, Hirakawa× Liu, Cuihua× Taishin, Akiyama× P. Engelward, Bevin× A. Nickoloff, Jac× Masao, Suzuki× Bing, Wang× Mitsuru, Nenoi× Sei, Sai× Akira, Fujimori× Hirokazu, Hirakawa× Liu, Cuihua× Masao, Suzuki× Bing, Wang× Mitsuru, Nenoi× Sei, Sai |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | In this study, we aimed to investigate how homologous recombinant (HR)-related genomic instability is involved in ionizing radiation (IR)-induced thymic lymphoma in mice. We divided five-week-old Rosa26 Direct Repeat- GFP (RaDR-GFP) transgenic mice into non-IR control and IR groups and exposed the mice in the IR group to a 7.2 Gy dose of γ-rays, delivered in 1.8 Gy fractions, once a week for four weeks. We then estimated mouse survival and recorded their body, thymus, and spleen weights. The frequency of HR events in the chromosomes of the thymus, bone marrow, and spleen cells and the phenotype of thymic lymphoma cells were analyzed using fluorescence- activated cell sorting (FACS). We found that most mice in the IR group developed thymic lymphoma, their survival rate decreasing to 20% after 180 days of IR exposure, whereas no mice died in the non-IR control group until day 400. The thymus and spleen weighed significantly more in the IR-4-month group than that in the non-IR group; however, we observed no significant differences between the body weights of the control and IR mice. FACS analysis indicated that the frequency of HR events significantly increased at two and four months after the last IR dose in the bone marrow and thymus cells, but not in the spleen cells of RaDR-GFP transgenic mice, suggesting that recombi- nant cells accumulated in the thymus upon IR exposure. This suggests that IR induces genome instability, revealed as increased HR, that drives the development of thymic lymphoma. Additionally, phenotypic analysis of lymphoma cells showed an increase in the CD4-/CD8+ (CD8SP) cell population and a decrease in the CD4+/CD8- (CD4SP) cell population in the IR-4-month group compared to that in the non-IR group, indicating that IR induces an aberrant cell phenotype characteristic of lymphoma. In conclusion, we observed a significant increase in HR events and abnormal phenotype in thymic lymphoma cells at two and four months after IR exposure in both the thymus and bone marrow tissues, suggesting that genomic instability is involved in the early stages of thymic lymphomagenesis. Our study indicates that HR-visualizing RaDR-GFP transgenic mice can help explore the links between the molecular mecha- nisms of genome instability and IR-induced tumorigenesis. | |||||
| 書誌情報 |
American Journal of Cancer Research 巻 12, 号 2, p. 562-573, 発行日 2022-02 |
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| 出版者 | ||||||
| 出版者 | e-Century Publishing Corporation | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2156-6976 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899999/ | |||||
