Department of Genetics, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social (IMSS), Monterrey, Nuevo León, Mexico.
Faculty of Biological Sciences, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Methods Mol Biol. 2024;2784:271-284. doi: 10.1007/978-1-0716-3766-1_18.
Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.
基因组不稳定性是宫颈癌进展的一个重要生物标志物。DBD-FISH(DNA 断裂检测-荧光原位杂交)是一种敏感的方法,可检测宫颈上皮细胞中的链断裂、碱不稳定位点和不完全的 DNA 切除修复。该技术将阴道病变刮取物中细胞的微凝胶浸泡和 DNA 解旋处理与 FISH 的能力集成到数字图像分析中。在琼脂糖基质中捕获的细胞被裂解并浸泡在碱性解旋溶液中,该溶液在内部 DNA 链断裂的末端产生单链 DNA 基序。中和后,微凝胶脱水,并用 DNA 标记的探针孵育细胞。目标序列处杂交探针的数量与解旋步骤中产生的单链 DNA 的量相对应,这相当于局部 DNA 断裂的程度。DNA 损伤并非均匀分布在细胞的整个 DNA 中,而是局限于特定的染色体位点。本章提供了该技术的概述,重点介绍了其评估特定序列中 DNA 损伤与宫颈癌进展阶段之间关联的能力。