期刊
REPRODUCTIVE TOXICOLOGY
卷 30, 期 3, 页码 457-468出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2010.05.014
关键词
Gene Ontology; In vitro toxicology; Microarray; Mouse embryo; Neural tube defects; Teratogen; Toxicogenomics; Valproic acid
资金
- Swedish Animal Welfare Agency
- AstraZeneca
Cell-based in vitro assays would potentially reduce animal testing in preclinical drug development. Mouse embryos exposed to the teratogenic drug valproic acid (VPA) in utero for 1, 5, 3 or 6 h on gestational day 8 were analyzed using microarrays. Significant effects on gene expression were observed already at 1.5 h, and 85 probes were deregulated across all time points. To find transcriptional markers of VPA-induced developmental toxicity, the in vivo data were compared to previous in vitro data on embryonal carcinoma P19 cells exposed to VPA for 1.5, 6 or 24 h. Maximal concordance between embryos and cells was at the 6h time points, with 163 genes showing similar deregulation. Developmentally important Gene Ontology terms, such as organ morphogenesis and tube development were overrepresented among putative VPA target genes. The genes Gja1, Hap1, Sall2, H1f0, Cyp26a1, Fgf15, Otx2, and Lin7b emerged as candidate in vitro markers of potential VPA-induced teratogenicity. (C) 2010 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据