Powell James Rees, Bennett Mark Richard, Evans Katie Ellen, Yu Shirong, Webster Richard Michael, Waters Raymond, Skinner Nigel, Reed Simon Huw
Cancer &Genetics Building, Cardiff University, School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Agilent Technologies (UK) Ltd, 710 Wharfedale Road, Winnersh Triangle, Wokingham, Berkshire, RG41 5TP, UK.
Sci Rep. 2015 Jan 22;5:7975. doi: 10.1038/srep07975.
Genotoxins cause DNA damage, which can result in genomic instability. The genetic changes induced have far-reaching consequences, often leading to diseases such as cancer. A wide range of genotoxins exists, including radiations and chemicals found naturally in the environment, and in man-made forms created by human activity across a variety of industries. Genomic technologies offer the possibility of unravelling the mechanisms of genotoxicity, including the repair of genetic damage, enhancing our ability to develop, test and safely use existing and novel materials. We have developed 3D-DIP-Chip, a microarray-based method to measure the prevalence of genomic genotoxin-induced DNA damage. We demonstrate the measurement of both physical and chemical induced DNA damage spectra, integrating the analysis of these with the associated changes in histone acetylation induced in the epigenome. We discuss the application of the method in the context of basic and translational sciences.
基因毒素会导致DNA损伤，进而可能导致基因组不稳定。所诱导的基因变化具有深远影响，常常会引发诸如癌症等疾病。存在多种基因毒素，包括环境中天然存在的辐射和化学物质，以及各行业人类活动产生的人造形式。基因组技术为揭示基因毒性机制提供了可能，包括基因损伤的修复，增强了我们研发、测试及安全使用现有和新型材料的能力。我们开发了3D-DIP-Chip，这是一种基于微阵列的方法，用于测量基因组基因毒素诱导的DNA损伤的发生率。我们展示了对物理和化学诱导的DNA损伤谱的测量，并将这些分析与表观基因组中诱导的组蛋白乙酰化相关变化相结合。我们在基础科学和转化科学的背景下讨论了该方法的应用。
