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利用健康类器官体系在动物和人类之间架起环境化学物毒理学性质的桥梁。

Bridging toxicological properties of environmental chemicals between animals and humans using healthy organoid systems.

机构信息

Central Animal Division, National Cancer Center Research Institute.

Present address: Translational Research Division, Central Institute for Experimental Medicine and Life Science.

出版信息

J Toxicol Sci. 2024;49(10):425-434. doi: 10.2131/jts.49.425.

Abstract

The application of organoids derived from animal tissues and human-induced pluripotent stem cells to safety assessments of environmental chemicals has been introduced over the last decade. One of the objectives of this approach is to develop an alternative method for animal toxicological studies, while another is to focus on the local reactions of chemicals in each organ/tissue. One of the most important goals is bridging the toxicological properties of chemicals between animals and humans, which may be compared on a level playing field using healthy organoids derived from both animals and humans in vitro, excluding species difference in the absorption, distribution, metabolism, and excretion properties of chemicals in vivo. An overview of the application of organoid systems to safety assessments of environmental chemicals, including general toxicology, developmental toxicology, carcinogenicity, and mutagenicity, was provided herein, and bridging strategies using both animal and human organoids are proposed as a future perspective.

摘要

在过去十年中,已经将源自动物组织和人诱导多能干细胞的类器官应用于环境化学物的安全性评估中。该方法的目的之一是开发动物毒理学研究的替代方法,另一个目的是关注每种器官/组织中化学物质的局部反应。最重要的目标之一是在动物和人类之间架起化学物质毒理学特性的桥梁,这可以通过使用体外培养的来自动物和人类的健康类器官来实现,从而排除了体内化学物质吸收、分布、代谢和排泄特性的物种差异。本文概述了类器官系统在环境化学物安全性评估中的应用,包括一般毒理学、发育毒理学、致癌性和致突变性,并提出了使用动物和人类类器官的桥接策略作为未来的展望。

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