Proteomic analysis and in vitro developmental toxicity tests for mechanism-based safety evaluation of chemicals
Proteomic analysis and in vitro developmental toxicity tests for mechanism-based safety evaluation of chemicals
复制标题
基于机制的化学品安全性评价的蛋白质组学分析和体外发育毒性测试
DOI：
10.1586/epr.11.16
复制
发表时间：
2011
影响因子：
3.4
通讯作者：
K. Mitsunaga
中科院分区：
文献类型：
--
作者：
M. Usami;K. Mitsunaga
评估：Groebe K、Hayess K、Klemm-Manns M 等人。用于胚胎毒性体外测试的蛋白质生物标志物。 J.蛋白质组研究。 9(11), 5727–5738 (2010)。基于机制的安全性评估和减少动物使用是最近发育毒理学中的重要问题。蛋白质组分析的体外发育毒性测试是解决这些问题最有希望的解决方案。格罗贝等人。系统地将蛋白质组学分析应用于胚胎干细胞测试（一种经过验证的体外发育毒性测试），并发现从各种毒性类别中选择的模型测试化学品会诱导蛋白质表达变化。对所有具有表达变化的蛋白质进行聚类分析，将测试化学品分为两组：高胚胎毒性化学品和无或弱胚胎毒性化学品。此外，还鉴定了一些已知参与正常发育的候选蛋白质生物标志物。尽管需要进一步的机制研究，但使用体外发育毒性测试和蛋白质组分析将有助于在最少使用动物的情况下进行基于机制的安全性评估。
Evaluation of: Groebe K, Hayess K, Klemm-Manns M et al. Protein biomarkers for in vitro testing of embryotoxicity. J. Proteome Res. 9(11), 5727–5738 (2010). Mechanism-based safety evaluation and reduction of animal use are important issues in recent developmental toxicology. In vitro developmental toxicity tests with proteomic analysis are the most promising solution to these issues. Groebe et al. systematically applied proteomic analysis to the embryonic stem cell test, a validated in vitro developmental toxicity test, and found protein-expression changes induced by model test chemicals selected from various categories of toxicity. Cluster analysis of all the proteins with expression changes classified the test chemicals into two groups: highly embryotoxic chemicals and non- or weakly embryotoxic chemicals. In addition, some protein biomarker candidates that were known to be involved in normal development were identified. Although further mechanistic investigations are needed, the use of in vitro developmental toxicity tests with proteomic analysis will contribute to mechanism-based safety evaluation with minimal use of animals.