Radiation Biophysics Division, Nuclear Medicine Department, iThemba LABS.
Department of Biotechnology, University of the Western Cape.
J Vis Exp. 2021 Dec 25(178). doi: 10.3791/62623.
Ionizing radiation is a potent inducer of DNA damage and a well-documented carcinogen. Biological dosimetry comprises the detection of biological effects induced by exposure to ionizing radiation to make an individual dose assessment. This is pertinent in the framework of radiation emergencies, where health assessments and planning of clinical treatment for exposed victims are critical. Since DNA double strand breaks (DSB) are considered to be the most lethal form of radiation-induced DNA damage, this protocol presents a method to detect DNA DSB in blood samples. The methodology is based on the detection of a fluorescent labelled phosphorylated DNA repair protein, namely, γ-H2AX. The use of an automated microscopy platform to score the number of γ-H2AX foci per cell allows a standardized analysis with a significant decrease in the turn-around time. Therefore, the γ-H2AX assay has the potential to be one of the fastest and sensitive assays for biological dosimetry. In this protocol, whole blood samples from healthy adult volunteers will be processed and irradiated in vitro in order to illustrate the usage of the automated and sensitive γ-H2AX foci assay for biodosimetry applications. An automated slide scanning system and analysis platform with an integrated fluorescence microscope is used, which allows the fast, automatic scoring of DNA DSB with a reduced degree of bias.
电离辐射是一种强有力的 DNA 损伤诱导剂,也是一种有充分文献记录的致癌物质。生物剂量学包括检测因暴露于电离辐射而引起的生物效应,以进行个体剂量评估。这在辐射紧急情况下非常重要,因为对暴露受害者进行健康评估和临床治疗计划至关重要。由于 DNA 双链断裂 (DSB) 被认为是最致命的辐射诱导 DNA 损伤形式,因此本方案提出了一种在血液样本中检测 DNA DSB 的方法。该方法基于检测荧光标记的磷酸化 DNA 修复蛋白,即 γ-H2AX。使用自动化显微镜平台对每个细胞中的 γ-H2AX 焦点数量进行评分,可实现标准化分析,并显著缩短周转时间。因此,γ-H2AX 测定法有可能成为最快和最敏感的生物剂量学测定法之一。在本方案中,将处理来自健康成年志愿者的全血样本,并在体外进行辐照,以说明自动化和敏感的 γ-H2AX 焦点测定法在生物剂量学应用中的使用。使用了带有集成荧光显微镜的自动化载玻片扫描系统和分析平台,可快速、自动地对 DNA DSB 进行评分,并且偏差程度降低。