| 王晶,张亚平,丁德芳,高赟,张旭霞,张俊香,陈红红.γ-H2AX用于辐射生物剂量计研究的动物模型评价[J].中华放射医学与防护杂志,2015,35(5):329-333 |
| γ-H2AX用于辐射生物剂量计研究的动物模型评价 |
| Evaluation of applying γ-H2AX as a radiation biodosimetry with an animal model |
| 投稿时间：2015-01-23 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.05.003 |
| 中文关键词: γ射线 淋巴细胞 γ-H2AX pATM(S1981) pDNA-PKcs(T2609) |
| 英文关键词:γ-rays lymphocytes γ-H2AX pATM(S1981) pDNA-PKcs(T2609) |
| 基金项目:国家自然科学基金(81273000) |
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| 中文摘要: |
| 目的 通过比较γ射线照射诱导大鼠和人淋巴细胞DNA双链断裂(DSBs)修复动力学的变化,评价大鼠用于γ-H2AX焦点辐射生物剂量计动物模型的可行性. 方法 采用γ射线外照射Sprague-Dawley (SD)雄性大鼠和健康成人外周血淋巴细胞以及整体照射大鼠,分别于照射后不同时间采用免疫荧光技术检测DSBs分子标志物γ-H2AX焦点的变化,检测修复蛋白pATM(S1981)和pDNA-PKcs (T2609) 焦点的形成,以及它们与γ-H2AX焦点的共定位情况.结果0.5 Gy γ射线照射诱发大鼠和人淋巴细胞γ-H2AX焦点形成和消除动力学相一致,表现为受照后30 min,γ-H2AX焦点形成达到最大值(t大鼠=62.64,t人=28.52,P<0.05),6 h内快速下降 (t大鼠=45.96,t人=14.80,P<0.05),至受照后24 h残留焦点数为最大值的3%~8%.γ射线照射后30 min,大鼠和人淋巴细胞pATM (S1981)和pDNA-PKcs (T2609)焦点形成数较未照射对照组显著增加 (t大鼠=21.05、25.80,t人=11.07、29.52,P<0.05),分别与γ-H2AX焦点共定位比例亦显著升高 (t大鼠=5.34、9.14,t人=18.32、51.28,P<0.05),占26%~32%.离体照射和整体照射诱导大鼠淋巴细胞γ-H2AX焦点形成数相一致,而且γ-H2AX焦点形成与照射剂量之间呈良好的线性关系.结论 大鼠为γ-H2AX用于辐射生物剂量计研究提供了很好的动物模型,ATM与DNA-PKcs共激活在辐射诱导大鼠和人淋巴细胞DSBs的修复中发挥重要的作用. |
| 英文摘要: |
| Objective To evaluate the potential feasibility of γ-H2AX foci as a biodosimetry after exposure to ionizing radiation by comparing DNA double-strand break repair kinetics in rat blood lymphocytes with that in human lymphocytes. Methods Peripheral blood lymphocytes separated from Sprague-Dawley(SD) male rats and healthy adults were exposed to γ-rays, and some rats were also subjected to total body irradiation. The inductions of DNA repair-related foci of γ-H2AX, pATM (S1981) and pDNA-PKcs (T2609) were detected with immunofluorescence staining technique at different time points post-irradiation, and the status of their co-localization was analyzed.Results The induction kinetics of γ-H2AX foci in rat lymphocytes was similar to that observed in human lymphocytes. The frequencies of γ-H2AX foci peaked at 30 min after γ-ray irradiation (trat=62.64, thuman=28.52,P<0.05), then decreased rapidly after 6 h post-irradiation (trat=45.96, thuman=14.80,P<0.05), and the residual foci number remained only about 3%-8% of its maximal value at 24 h post-irradiation. At 30 min after γ-ray irradiation,the frequencies of pATM (S1981) and pDNA-PKcs (T2609) foci in rat and human lymphocytes significantly higher than those of nonirradiated control (trat=21.05, 25.80, thuman=11.07, 29.52,P<0.05),and the frequencies of co-localization of pATM (S1981) or pDNA-PKcs (T2609) foci with γ-H2AX foci also markedly increased by 26%-32% in irradiated lymphocytes of rat and human (trat=5.34, 9.14, thuman=18.32, 51.28,P<0.05). Moreover, γ-H2AX foci incidence in rat lymphocytes in vitro was consistent with that induced by total body irradiation of rat. The number of γ-H2AX foci in irradiated rat lymphocytes increased with irradiation dose in a linear dose-dependent manner, its slope was similar to that of irradiated human lymphocytes reported by other laboratory. Conclusions Rat is a useful animal model to evaluate radiation biodosimetry with γ-H2AX foci in lymphocytes. The co-activation of ATM and DNA-PK plays an important role in DSB repair in the irradiated lymphocytes of rat and human. |
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