Experiments exploring the effects of TCE on cardiac development in the chicken embryo showed an unusual dose response curve where exposure in ovo produced more pronounced molecular effects on cardiac function at lower doses than at greater concentrations. Dr. Runyan explored the expression of cytochrome p450 and UGTA1 enzymes in the whole embryo and found that TCE failed to induce any of the avian homologues normally associated with TCE metabolism of the liver.
The hypothesis to be tested was that HNF4a is a target of TCE. Bioinformatic analysis had suggested that this transcription factor was the most highly-linked molecule to the genes altered by TCE in a chick heart model. The study section had requested that we provide experimental data to back this up. Two approaches were taken. First we used cell culture with human HepG2 and mouse epicardial cells and selected a panel of 11 genes that were altered by TCE in mice and chicks. We then tested two molecules identified as an antagonist (Bi 6015) and an antagonist (Benflorex). Both reagents a