Advance Access publication July 26, 2008 PCB126 Exposure Disrupts ZebraFish Ventricular and Branchial but Not Early Neural Crest Development

We have used zebrafish and 3,3#,4,4#,5-pentachlorobiphenyl (PCB126) to investigate the developmental toxicity of polychlori-nated biphenyls (PCBs) that exert their effects through the aryl hydrocarbon receptor (AHR). We found that cardiac and neural crest (NC)–derived jaw and branchial cartilages are specifically targeted early in development. The suite of malformations, which ultimately leads to circulatory failure, includes a severely dysmorphic heart with a reduced bulbus arteriosus and abnormal atrioventricular and outflow valve formation. Early NC migration and patterning of the jaw and branchial cartilages was normal. However, the jaw and branchial cartilages failed to grow to normal size. In the heart, the ventricular myocardium showed a reduction in cell number and size. The heart and jaw/branchial phenotype could be rescued by pifithrin-a, a blocker of p53. However, the function of pifithrin-a in this model may act as a competitiv