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测定 DNA 修复能力的分析方法。

Assays to determine DNA repair ability.

机构信息

Toxicology Unit, Department of Psychobiology, University of A Coruña, A Coruña, Spain.

出版信息

J Toxicol Environ Health A. 2011;74(15-16):1094-109. doi: 10.1080/15287394.2011.582320.

Abstract

DNA repair is crucial to the integrity of the human genome since mammalian cells are continuously exposed to different chemical and physical genotoxic agents. To counteract the lesions induced by these agents, organisms have developed a number of highly conserved repair mechanisms involving numerous protein complexes grouped in several different repair pathways. The importance of studying the individual capacity to repair DNA damage lies in the observation that deficient repair mechanisms of the genome have been linked to the presence of large number of diseases and cancer, and alterations in these mechanisms may also alter the susceptibility of individuals exposed to a particular mutagen. This review focused on the current knowledge of different assays developed to evaluate DNA repair capacity (DRC). These assays, which are grouped into five major categories, have been successfully applied in (1) in vitro studies, (2) epidemiological studies in patients with cancer or other different pathologies, and (3) environmentally or occupationally exposed populations. Nevertheless, some of the limitations include high interlaboratory variability and difficulty to implement the assays on a large scale. The selection of an adequate DRC assay needs to be made on the basis of the objective raised for its application and taking into account a number of determining factors, namely, (1) speed and cost, (2) type of DNA repair to be evaluated, and (3) sample availability.

摘要

DNA 修复对于人类基因组的完整性至关重要,因为哺乳动物细胞会持续暴露于各种化学和物理遗传毒性物质中。为了对抗这些物质引起的损伤,生物已经开发了许多高度保守的修复机制,涉及许多蛋白质复合物,这些复合物被分组到几种不同的修复途径中。研究个体修复 DNA 损伤的能力非常重要,因为人们已经观察到基因组中存在缺陷的修复机制与大量疾病和癌症的发生有关,而这些机制的改变也可能改变个体对特定诱变剂的敏感性。这篇综述重点介绍了目前评估 DNA 修复能力 (DRC) 的不同检测方法的知识。这些检测方法被分为五类,已经成功应用于:(1) 体外研究;(2) 癌症或其他不同病理患者的流行病学研究;(3) 暴露于环境或职业中的人群。然而,其中一些局限性包括实验室间的高度变异性和在大规模上实施检测的困难。选择合适的 DRC 检测方法需要根据其应用的目的,并考虑到许多决定因素来进行,即:(1) 速度和成本;(2) 要评估的 DNA 修复类型;(3) 样本的可用性。

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