RT Journal Article
SR Electronic
T1 Antisense Evidence for Nuclear Factor-κB–Dependent Embryopathies Initiated by Phenytoin-Enhanced Oxidative Stress
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 404
OP 412
VO 66
IS 3
A1 Julia C. Kennedy
A1 Sylvie Memet
A1 Peter G. Wells
YR 2004
UL http://molpharm.aspetjournals.org/content/66/3/404.abstract
AB 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.