Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Lombardia, Italy.
SD Chemical and Physical Health Risks, Sciensano, Brussels, Belgium.
Methods Mol Biol. 2022;2425:185-200. doi: 10.1007/978-1-0716-1960-5_8.
Due to the link with serious adverse health effects, genotoxicity is an important toxicological endpoint in each regulatory setting with respect to human health, including for pharmaceuticals. To this extent, a compound potential to induce gene mutations as well as chromosome damage needs to be addressed. For chromosome damage, i.e., the induction of structural or numerical chromosome aberrations, several in vitro and in vivo test methods are available. In order to rapidly collect toxicological data without the need for test material, several in silico tools for chromosome damage have been developed over the last years. In this chapter, a battery of freely available in silico chromosome damage prediction tools for chromosome damage is applied on a dataset of pharmaceuticals. Examples of the different outcomes obtained with the in silico battery are provided and briefly discussed. Furthermore, results for coumarin are presented in more detail as a case study. Overall, it can be concluded that although they are in general less developed than those for mutagenicity, in silico tools for chromosome damage can provide valuable information, especially when combined in a battery.
由于与严重的健康影响有关，遗传毒性是与人类健康相关的每个监管环境中的一个重要毒理学终点，包括药物。在这方面，需要解决化合物引起基因突变和染色体损伤的潜力。对于染色体损伤，即诱导结构性或数量性染色体畸变，有几种体外和体内测试方法可用。为了在不需要测试材料的情况下快速收集毒理学数据，近年来已经开发了几种用于染色体损伤的计算工具。在本章中，应用了一组免费的可用于染色体损伤的计算染色体损伤预测工具，对一组药物数据集进行了分析。提供了不同的计算电池结果的例子，并进行了简要讨论。此外，还详细介绍了香豆素的结果作为案例研究。总的来说，可以得出结论，尽管它们通常不如致突变性的工具发达，但用于染色体损伤的计算工具可以提供有价值的信息，尤其是在组合使用时。
