Tissue-specific effects of valproic acid on DNA repair genes and apoptosis in postimplantation mouse embryos.

摘要: Exposure to the anticonvulsant drug valproic acid (VPA) is associated with an increased risk of congenital malformations. Although mechanisms contributing its teratogenicity are poorly understood, VPA has been shown induce DNA double strand breaks (DSB) and increase homologous recombination in vitro. The objective present study was determine whether utero exposure alters frequency intrachromosomal expression several genes involved DSB repair pKZ1 mouse embryos. Pregnant transgenic mice (GD 9.0) were administered (500 mg/kg s.c.) embryos extracted microdissected into head, heart, trunk regions 1, 3, 6, 24 h after injection. Quantitative PCR used measure tissue-specific lacZ, a surrogate recombination, Xrcc4, Rad51, Brca1, Brca2, Western blotting quantify cleaved caspase-3 cleaved-PARP protein. Increased only observed embryonic head following 6-h exposure. had no effect on Xrcc4 expression. Brca2 rapidly decreased tissues 1-h exposure, followed by subsequent all tissues, although it generally attenuated not due differences endogenous levels. Cleaved 3 This indicates that altered may be apoptosis.