DNA损伤标志物γ-H2AX及其在毒性测试应用中的研究进展  

Advances in DNA damage markerγ-H2AX and its toxicity testing applications

作　　者：瞿敏敏 陈佳 郭磊 徐华 谢剑炜 QU Min-min;CHEN Jia;GUO Lei;XU Hua;XIE Jian-wei(State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2021年第6期401-411,共11页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点研发计划(2018YFC1602600);国家自然科学基金(21974151)。

摘　　要：当DNA受到攻击尤其是发生DNA双链断裂(DSB)后,组蛋白H2AX的139位丝氨酸迅速磷酸化,生成磷酸化H2AX即γ-H2AX。γ-H2AX在DSB位点大量聚集并形成焦点,参与DNA的损伤修复,且γ-H2AX焦点数与DSB数量成正比。目前研究表明,γ-H2AX是表征DNA损伤的特异性生物标志物,可作为基因毒性的特异性效应指标。旨在检测γ-H2AX的试验(简称γ-H2AX试验)已被应用于众多与DNA损伤相关的基础研究和医学诊断中。本文介绍γ-H2AX的生成及生物学意义,论述基于免疫化学技术及质谱技术的γ-H2AX试验在体外基因毒性评价中的应用、γ-H2AX试验与其他基因毒性试验的性能对比及γ-H2AX与其他毒性终点标志物的互补性,并对γ-H2AX试验在基因毒性风险评估中的应用前景予以展望。The H2AX histone protein is rapidly phosphorylated at the serine-139 position to formγ-H2AX in response to a broad range of DNA damage,especially after DNA double-strand breaks(DSBs).γ-H2AX accumulates around DSB sites and forms a focus that participates in DNA damage repair.The number ofγ-H2AX foci is proportional to the number of DSBs.γ-H2AX is a recently-acknowledged attractive biomarker for evaluating DNA damage and can be used as a specific effect indicator for genotoxicity.The assay designed to detectγ-H2AX(referred to asγ-H2AX assay)has been used in multiple DNA damage related fields such as basic research and medical diagnosis.By combining domestic and foreign literature,this review outlines the formation and biological significance ofγ-H2AX,summarizes the applications ofγ-H2AX assay based on immunochemistry and mass spectrometry in in vitro genotoxicity evaluation,the performance comparison ofγ-H2AX assay and other genotoxicity assays,and complementation ofγ-H2AX with other toxicity endpoint markers,and discusses prospects ofγ-H2AX assay in genotoxicity risk assessment.

关 键 词：DNA双链断裂 组蛋白H2AX γ-H2AX试验 基因毒性 

分 类 号：R994[医药卫生—毒理学] R595[医药卫生—药学]