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形态发生系统与胚胎毒性筛选

Morphogenetic systems and screening for embryotoxicity.

作者信息

Jelínek R, Rychter Z

出版信息

Arch Toxicol Suppl. 1980;4:267-73. doi: 10.1007/978-3-642-67729-8_54.

Abstract

While mutagenesis appears to be a single-cell phenomenon, the target for teratogenesis are the groups of cell populations constituting the morphogenetic system (MGS). The sensitivity of MGSs is of two kinds. First, it is the sensitivity to general cytotoxic agents. It is non-specific and reaches its maximum during early embryogenesis. The second type of sensitivity manifests itself at the more advanced stages of development, and it is intimately connected with the specific cell differentiation. The basic parameters of embryotoxicity can be estimated from the direct exposure of the selected MGSs both to the test substance and to its metabolites occurring in man. Based upon these principles a rapid and inexpensive screening test (CHEST) has been introduced using the embryonic chick. The test is capable of demonstrating the embryotoxicity effect level, the gross dose-effect relationships as well as estimating the general type of embryotoxic action. The predictive value of this procedure is comparable to that of the current routine techniques. A multilevel combined test for embryotoxicity is proposed in which CHEST is engaged as a priority selection system.

摘要

虽然诱变似乎是一种单细胞现象,但致畸作用的靶标是构成形态发生系统(MGS)的细胞群体组。MGS的敏感性有两种。首先,是对一般细胞毒性剂的敏感性。它是非特异性的,在胚胎发育早期达到最大值。第二种敏感性表现在发育的更高级阶段,并且与特定的细胞分化密切相关。胚胎毒性的基本参数可以通过将选定的MGS直接暴露于受试物质及其在人体中产生的代谢物来估计。基于这些原理,已经引入了一种使用胚胎鸡的快速且廉价的筛选试验(CHEST)。该试验能够证明胚胎毒性效应水平、总剂量 - 效应关系以及估计胚胎毒性作用的一般类型。该程序的预测价值与当前常规技术相当。提出了一种用于胚胎毒性的多级联合试验,其中CHEST作为优先选择系统。

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