TY - JOUR T1 - Antisense Evidence for Nuclear Factor-κB–Dependent Embryopathies Initiated by Phenytoin-Enhanced Oxidative Stress JF - Molecular Pharmacology JO - Mol Pharmacol SP - 404 LP - 412 VL - 66 IS - 3 AU - Julia C. Kennedy AU - Sylvie Memet AU - Peter G. Wells Y1 - 2004/09/01 UR - http://molpharm.aspetjournals.org/content/66/3/404.abstract N2 - Endogenous and xenobiotic-enhanced oxidative stress may initiate embryonic death and birth defects via reactive oxygen species (ROS) signaling pathways involving nuclear transcription factor-κB (NF-κB). Using embryo culture and a transgenic mouse engineered with a NF-κB–dependent β-galactosidase reporter gene, we employed NF-κB antisense oligonucleotide therapy to determine whether NF-κB signaling contributes to the embryopathic effects of the ROS-initiating teratogen phenytoin. Phenytoin selectively increased NF-κB activity in target tissues and caused embryopathies, both of which were blocked by NF-κB antisense oligonucleotides but not by sense and nonsense oligonucleotide controls. NF-κB signaling may therefore contribute to the mechanism of ROS-mediated embryopathies. ER -