基于类胚体面积的先进发育毒性测试方法。
Advanced developmental toxicity test method based on embryoid body's area.
机构信息
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea; Predictive Model Research Center, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
出版信息
Reprod Toxicol. 2017 Sep;72:74-85. doi: 10.1016/j.reprotox.2017.06.185. Epub 2017 Jun 30.
Embryonic stem cell test (EST) evaluates the embryotoxic potential of substances and measures the half inhibition in viability of mouse embryonic stem cells (ESCs), fibroblasts (3T3 cells) and in cardiac differentiation of ESC. In this study, we suggest the developmental toxicity test method (termed EBT) applying area of embryoid bodies (EBs) instead of cardiac differentiation of EST. In the assessment of 21 substances, EB area was logarithmically decreased in dose-dependent manner. Decline in EB area resulted in decrease of beating ratio during differentiation of ESCs. In classification by the EBT-based prediction model reflecting decline in cell viability and EB area, toxicity for 21 chemicals showed 90.5% accuracy. In the results of next generation sequencing, reduction in EB area resulted from cell cycle arrest mediated by HDAC2 and CDKN2A. Conclusively, EBT is advanced and is a useful tool to assess and classify various embryotoxicants in a short time with less effort.
胚胎干细胞测试（EST）评估物质的胚胎毒性潜力，并测量小鼠胚胎干细胞（ESCs）、成纤维细胞（3T3 细胞）的活力半抑制和 ESC 的心脏分化。在这项研究中，我们建议使用拟胚体（EBs）的面积来代替 EST 的心脏分化，作为发育毒性测试方法（EBT）。在对 21 种物质的评估中，EB 面积呈剂量依赖性的对数减少。EB 面积的减少导致 ESC 分化过程中心跳比例的下降。根据反映细胞活力和 EB 面积下降的基于 EBT 的预测模型进行分类，21 种化学物质的毒性显示出 90.5%的准确性。在下一代测序的结果中，EB 面积的减少是由 HDAC2 和 CDKN2A 介导的细胞周期停滞引起的。总之，EBT 是一种先进的方法，是一种在短时间内用较少的努力评估和分类各种胚胎毒性物质的有用工具。
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