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γ-H2AX用于辐射生物剂量计研究的动物模型评价
  • ISSN号:0254-5098
  • 期刊名称:《中华放射医学与防护杂志》
  • 时间:0
  • 分类:R144.1[医药卫生—公共卫生与预防医学]
  • 作者机构:[1]复旦大学放射医学研究所,上海200032
  • 相关基金:国家自然科学基金(81273000)
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 Gyγ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),6h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 (trst =62.64,th =28.52,P 〈 0.05),then decreased rapidly after 6 h post-irradiation (trat =45.96,th =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,th =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

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期刊信息
  • 《中华放射医学与防护杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市德外新康街2号
  • 邮编:100088
  • 邮箱:cjrmp@cjrmp.sina.net
  • 电话:010-62389620
  • 国际标准刊号:ISSN:0254-5098
  • 国内统一刊号:ISSN:11-2271/R
  • 邮发代号:18-93
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:11741