Hadi Naji Said Aboud, Stopper Helga
Institute of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Strasse 9, 97078 Würzburg, Germany; School of Health and Human Sciences, Pwani University, Kilifi, Kenya.
Institute of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Strasse 9, 97078 Würzburg, Germany.
Mutat Res Genet Toxicol Environ Mutagen. 2025 Jan;901:503839. doi: 10.1016/j.mrgentox.2024.503839. Epub 2024 Dec 12.
There has been a shift from traditional animal models towards alternative methods. While 2D cell culture has a decade long tradition, more advances methods like 3D cultures, organoids, and co-culture techniques, which better mimic in vivo conditions, are not yet well established in every research area. Genotoxicity assessment is an integral part of toxicological testing or regulatory approval of pharmaceuticals and chemicals. The micronucleus assay is now a standard method in this context. In this systematic literature review, we aim to describe the state of the art of the application of co-cultures of two mammalian cell lines for micronucleus assessment. We summarized the cell types used, methods for co-culture, disease models and agents, as well as the application of additional genotoxicity endpoints and viability tests. Airway system cells were the most frequent, followed by macrophage-like cells, liver cells, and various others. Co-culture techniques involve either direct physical contact or separation by porous membranes. Within a limited number of investigations using other genotoxicity assays like the comet and γH2AX assays in parallel, the micronucleus assay performed well. Overall, the micronucleus test demonstrating its suitability in disease models and for a more complex substance testing beyond simple 2D cultures, encouraging a more widespread use in co-culture systems in the future.
从传统动物模型向替代方法已经出现了转变。虽然二维细胞培养已有长达十年的传统，但像三维培养、类器官和共培养技术等更先进的方法，能更好地模拟体内条件，在每个研究领域尚未得到充分确立。遗传毒性评估是药物和化学品毒理学测试或监管批准不可或缺的一部分。在此背景下，微核试验现在是一种标准方法。在这项系统的文献综述中，我们旨在描述应用两种哺乳动物细胞系共培养进行微核评估的现状。我们总结了所使用的细胞类型、共培养方法、疾病模型和试剂，以及其他遗传毒性终点和活力测试的应用。气道系统细胞最为常见，其次是巨噬细胞样细胞、肝细胞和其他各种细胞。共培养技术涉及直接物理接触或通过多孔膜分离。在有限数量的同时使用其他遗传毒性试验如彗星试验和γH2AX试验的研究中，微核试验表现良好。总体而言，微核试验证明了其在疾病模型中的适用性以及用于超出简单二维培养的更复杂物质测试的适用性，鼓励未来在共培养系统中更广泛地使用。
