非洲爪蟾的蛙胚胎致畸试验及其与哺乳动物体内研究的预测性比较

Frog embryo teratogenesis assay on Xenopus and predictivity compared with in vivo mammalian studies.

作者信息

Leconte Isabelle, Mouche Isabelle

机构信息

Covance Laboratory SAS, Porcheville, France.

出版信息

Methods Mol Biol. 2013;947:403-21. doi: 10.1007/978-1-62703-131-8_29.

DOI:10.1007/978-1-62703-131-8_29

PMID:23138919

Abstract

Frog embryo teratogenesis assay on Xenopus (FETAX) has been routinely used in our laboratory for the last 12 years as a routine developmental toxicity screening test for pharmaceutical candidate compounds. To date, out of more than 400 candidates tested in FETAX, around 60 have also been evaluated in mammalian embryotoxicity studies according to standard ICH protocols.Compound teratogenic potential in both FETAX and mammalian embryotoxicity studies is determined after analysis of the developmental toxicity characterized by embryotoxicity, growth delay, and/or potential to induce malformations. Based on this experience, the predictivity of FETAX is 81% with a minimal proportion of false positive results.

摘要

在过去12年里，非洲爪蟾胚胎致畸试验（FETAX）在我们实验室一直被常规用作药物候选化合物的常规发育毒性筛选试验。迄今为止，在FETAX试验的400多种候选化合物中，约60种也已根据国际人用药品注册技术协调会（ICH）标准方案在哺乳动物胚胎毒性研究中进行了评估。在分析以胚胎毒性、生长延迟和/或诱导畸形可能性为特征的发育毒性后，确定FETAX和哺乳动物胚胎毒性研究中化合物的致畸潜力。基于这一经验，FETAX的预测率为81%，假阳性结果比例极小。