Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar 4710-057 Braga, Portugal.
Int J Environ Res Public Health. 2020 Mar 19;17(6):2046. doi: 10.3390/ijerph17062046.
Genotoxicity screening tests aim to evaluate if and to what extent a compound in contact with the human body (e.g., a drug molecule, a compound from the environment) interacts with DNA. The comet assay is a sensitive method used to predict the risk of DNA damage in individual cells, as it quantifies the tape breaks, being the alkaline version (pH > 13) the most commonly used in the laboratory. Epithelial cells serve as biomatrices in genotoxicity assessments. As ca. 80% of solid cancers are of epithelial origin, the quantification of the DNA damage upon exposure of epithelial cells to a drug or drug formulation becomes relevant. Comet assays run in epithelial cells also have clinical applications in human biomonitoring, which assesses whether and to what extent is the human body exposed to environmental genotoxic compounds and how such exposure changes over time. Ocular mucosa is particularly exposed to environmental assaults. This review summarizes the published data on the genotoxicity assessment in estimating DNA damage in epithelial cells with a special focus on ocular cell lines. General comet assay procedures for ex vivo and in vivo epithelium samples are also described.
致瘤性筛选试验旨在评估接触人体的化合物(例如药物分子、环境化合物)是否以及在何种程度上与 DNA 相互作用。彗星试验是一种用于预测个体细胞 DNA 损伤风险的敏感方法,因为它可以定量测定 DNA 链的断裂,其中碱性版本(pH 值>13)在实验室中最常用。上皮细胞作为致瘤性评估的生物基质。由于约 80%的实体瘤源自上皮组织,因此评估上皮细胞暴露于药物或药物制剂时的 DNA 损伤程度变得非常重要。在人类生物监测中,运行于上皮细胞的彗星试验也具有临床应用,用于评估人体是否以及在何种程度上暴露于环境遗传毒性化合物,以及这种暴露随时间的变化。眼黏膜特别容易受到环境攻击。本综述总结了已发表的关于用特殊的眼细胞系评估上皮细胞 DNA 损伤的致瘤性评估数据。还描述了用于体外和体内上皮组织样本的一般彗星试验程序。