Advances in three-dimensional (3D) cell culture technology have led to the development of more biologically and physiologically relevant models to study organ development, disease, toxicology and drug screening. Organoids have been derived from many mammalian tissues, both normal and tumour, from adult stem cells and from pluripotent stem cells. Tissue organoids can retain many of the cell types and much of the structure and function of the organ of origin. Organoids derived from pluripotent stem cells display increased complexity compared with organoids derived from adult stem cells. It has been shown that organoids express many functional xenobiotic-metabolising enzymes including cytochrome P450s (CYPs). This has benefitted the drug development field in facilitating pre-clinical testing of more personalised treatments and in developing large toxicity and efficacy screens for a range of compounds. In the field of environmental and genetic toxicology, treatment of organoids with various compounds has generated responses that are close to those obtained in primary tissues and in vivo models, demonstrating the biological relevance of these in vitro multicellular 3D systems. Toxicological investigations of compounds in different tissue organoids have produced promising results indicating that organoids will refine future studies on the effects of environmental exposures and carcinogenic risk to humans. With further development and standardised procedures, advancing our understanding on the metabolic capabilities of organoids will help to validate their use to investigate the modes of action of environmental carcinogens.

中文翻译：

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毒理学和遗传毒理学的类器官：药物应用和环境致癌前景


三维 (3D) 细胞培养技术的进步导致了更多生物学和生理学相关模型的开发，用于研究器官发育、疾病、毒理学和药物筛选。类器官来源于许多哺乳动物组织，包括正常组织和肿瘤组织、成体干细胞和多能干细胞。组织类器官可以保留许多细胞类型以及起源器官的许多结构和功能。与源自成体干细胞的类器官相比，源自多能干细胞的类器官表现出更高的复杂性。研究表明，类器官表达许多功能性外源代谢酶，包括细胞色素 P450（CYP）。这有利于药物开发领域，促进更个性化治疗的临床前测试，以及开发一系列化合物的大规模毒性和功效筛选。在环境和遗传毒理学领域，用各种化合物处理类器官产生的反应与原代组织和体内模型中获得的反应接近，证明了这些体外多细胞 3D 系统的生物学相关性。对不同组织类器官中化合物的毒理学研究产生了有希望的结果，表明类器官将完善未来关于环境暴露和人类致癌风险影响的研究。随着进一步的发展和标准化程序，加深我们对类器官代谢能力的理解将有助于验证它们在研究环境致癌物的作用模式方面的用途。