Drug Safety Sciences, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Reprod Toxicol. 2011 Sep;32(2):213-9. doi: 10.1016/j.reprotox.2011.06.119. Epub 2011 Jun 21.
The zebrafish embryotoxicity/teratogenicity assay is described as a useful alternative screening model to evaluate the effect of drugs on embryofoetal development. Fertilized eggs were exposed to different concentrations of 15 compounds with teratogenic (8) and non-teratogenic (7) potential until 96h post-fertilization when 28 morphological endpoints and the level of compound uptake was assessed. The majority of drugs testing positive in mammals was also positive in zebrafish (75% sensitivity), while a relative high number of false positives were noted (43% specificity). Compound uptake determination appears useful for clarifying classifications as teratogenic or potential overdose although assay sensitivity could be improved to 71% if the exposure threshold, previously suggested as ∼50ng/larvae, is reconsidered. The zebrafish assay shows some potential, though limited in its current form, as a screening tool for developmental toxicity within Janssen drug development. Further assay refinement with respect to endpoints and body burden threshold is required.
斑马鱼胚胎毒性/致畸性试验被描述为一种有用的替代筛选模型，可用于评估药物对胚胎胎儿发育的影响。受精后的卵子暴露于具有致畸性（8 种）和非致畸性（7 种）潜力的 15 种化合物的不同浓度中，直到受精后 96 小时，评估 28 种形态学终点和化合物摄取水平。在哺乳动物中检测为阳性的大多数药物在斑马鱼中也为阳性（敏感性为 75%），而假阳性的数量相对较高（特异性为 43%）。尽管如果重新考虑先前建议的暴露阈值（约 50ng/幼虫），则可以将检测灵敏度提高到 71%，但化合物摄取测定似乎对于澄清致畸性或潜在过量的分类有用。斑马鱼试验显示出一定的潜力，尽管在目前的形式下有限，可作为杨森药物开发中发育毒性的筛选工具。需要进一步完善终点和体内负荷阈值的试验。
