Panzica-Kelly Julieta M, Zhang Cindy X, Augustine-Rauch Karen
Discovery Toxicology, Bristol-Myers Squibb Company, Princeton, NJ, USA.
Methods Mol Biol. 2012;889:25-50. doi: 10.1007/978-1-61779-867-2_4.
A promising in vitro zebrafish developmental toxicology assay was generated to test compounds for their teratogenic potential. The assay's predictivity is approximately 87% in AB strain fish (Brannen KC et al., Birth Defects Res B Dev Reprod Toxicol 89:66-77, 2010). The procedure entails exposing dechorionated gastrulation-stage embryos to a range of compound concentrations for 5 days throughout embryonic and larva development. The larvae are evaluated for viability in order to identify an LC25 (the compound concentration in which 25% lethality is observed) and morphological anomalies using a numerical score system to identify the NOAEL (no observed adverse effect level). These values are used to calculate the teratogenic index (LC25/NOAEL ratio) of each compound. If the teratogenic index is equal to or greater than 10 then the compound is classified as a teratogen, and if the ratio is less than 10 then the compound is classified as a nonteratogen (Brannen KC et al., Birth Defects Res B Dev Reprod Toxicol 89:66-77, 2010).
已建立一种有前景的体外斑马鱼发育毒理学试验，用于测试化合物的致畸潜力。该试验在AB品系鱼类中的预测率约为87%（Brannen KC等人，《出生缺陷研究B：发育生殖毒理学》89:66 - 77，2010年）。该程序包括在胚胎和幼体发育的整个5天时间里，将去绒毛膜的原肠胚期胚胎暴露于一系列化合物浓度下。对幼体进行活力评估，以确定LC25（观察到25%致死率时的化合物浓度），并使用数字评分系统评估形态异常，以确定无观察到不良作用水平（NOAEL）。这些值用于计算每种化合物的致畸指数（LC25/NOAEL比值）。如果致畸指数等于或大于10，则该化合物被归类为致畸剂；如果该比值小于10，则该化合物被归类为非致畸剂（Brannen KC等人，《出生缺陷研究B：发育生殖毒理学》89:66 - 77，2010年）。
