کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2594058 1132257 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Early transcriptional responses in mouse embryos as a basis for selection of molecular markers predictive of valproic acid teratogenicity
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Early transcriptional responses in mouse embryos as a basis for selection of molecular markers predictive of valproic acid teratogenicity
چکیده انگلیسی

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 6-h 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Reproductive Toxicology - Volume 30, Issue 3, November 2010, Pages 457–468
نویسندگان
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