Molecular approaches to developmental malformations using analogous forms of valproic acid.
The teratogenic potential of valproic acid has been well established both in experimental models and in human clinical studies. Evidence from many previous studies has shown that VPA is an appropriate drug model for studying chemical structure-teratogenicity relationships. Using molecular techniques of DNA microarray (GeneChip system) or quantitative real-time polymerase chain reaction with low teratogenic VPA analogs as comparative control drugs, we attempted to identify the genes involved with the molecular mechanisms of VPA teratogenicity in the neural tube and the axial skeleton of the mouse embryo. The recent development of DNA microarray enables a genome-wide approach to the identification of genes correlated with the teratogenicity of chemicals (teratogenomics). The VPA-induced changes in gene expression seen during mouse embryogenesis provides information for understanding how VPA disrupts normal embryonic development, and also provides leads for the development of safer medicines.
Okada
Akinobu
A
Drug Safety Research Laboratories, Astellas Pharma, Yodogawa-ku, Osaka, Japan. akinobu.okada@jp.astellas.com
Fujiwara
Michio
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000013:Congenital Abnormalities / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D051379:Mice; D008822:Mice, Transgenic; D008956:Models, Chemical; D009154:Mutation; D009432:Neural Crest / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013997:Time Factors; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000927:Anticonvulsants; D014635:Valproic Acid