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使用鼠胚胎干细胞衍生类胚体的替代发育毒性试验的预验证研究。

Pre-validation study of alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies.

机构信息

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.

出版信息

Food Chem Toxicol. 2019 Jan;123:50-56. doi: 10.1016/j.fct.2018.10.044. Epub 2018 Oct 16.

DOI:10.1016/j.fct.2018.10.044
PMID:30339957
Abstract

The embryoid body test (EBT) is a developmental toxicity test method that assesses the half inhibitory concentrations of substances in the area of embryoid bodies (EBs), and in the viability of mouse embryonic stem cells (ESCs) and fibroblasts (3T3 cells) following chemical exposure for three and four days, respectively. In the previous study, the EBT showed more advanced than the embryonic stem cell test (EST) from the European Centre for the Validation of Alternative Methods (ECVAM) applying cardiac differentiation of mouse ESCs, because the EBT greatly reduced the exposure time, labor, and amount of materials required, and misclassification of embryotoxic potential. This pre-validation study evaluated the predictive accuracy of the EBT using 26 coded test substances by two steps: intra-laboratory and inter-laboratory reproducibility tests. Since some substances have different embryotoxic potentials at different pregnancy periods, in this study, a new prediction model consisting of non-toxic and toxic classes was used, instead of the existing prediction model assessing embryotoxicants in four classes. The results of the intra- and inter-laboratory tests were highly accurate (above 80%) when substances were classified using the predictive model. In conclusion, EBT can accurately classify various embryotoxicants in a short time with less effort and greater validation.

摘要

胚状体试验(EBT)是一种发育毒性测试方法,用于评估胚状体(EBs)区域中物质的半抑制浓度,以及化学暴露后分别在 3 天和 4 天内对小鼠胚胎干细胞(ESCs)和纤维母细胞(3T3 细胞)的存活率。在之前的研究中,EBT 显示出比欧洲替代方法验证中心(ECVAM)应用于心脏分化的胚胎干细胞试验(EST)更先进,因为 EBT 大大减少了暴露时间、劳动力和所需材料的数量,并且避免了胚胎毒性潜力的错误分类。这项预验证研究通过两步评估了 EBT 使用 26 种编码测试物质的预测准确性:实验室内部和实验室间的重现性测试。由于某些物质在不同的妊娠期间具有不同的胚胎毒性潜力,因此在本研究中,使用了一种新的预测模型,由无毒和有毒两类组成,而不是现有的预测模型评估四类胚胎毒性物质。当使用预测模型对物质进行分类时,实验室内部和实验室间测试的结果非常准确(超过 80%)。总之,EBT 可以在短时间内用更少的努力和更大的验证来准确分类各种胚胎毒性物质。

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