Superfund Research Program
Developmental Toxicity of non-Dioxin-like PCBs and Chemical Mixtures
Project investigators focused on the cloning, expression and functional characterization of several target cytochrome P450 genes. Novel CYP1 family genes initially assigned to CYP1B were confirmed as a new subfamily, CYP1C, in an alternate teleost fish model (scup). CYP1C genes were also identified in zebrafish and Fundulus. Novel CYP2 family genes in a new subfamily, CYP2AA, were also identified in zebrafish. CYP2AA1 and CYP2AA2 were cloned and expressed in COS cells and functional characterization begun. The CYP2AAs are hoped to be the elusive teleost CYP2B homologues. Chemical effects on expression have been studied with zebrafish cDNA microarrays developed in the lab. These results confirmed that CYP1A is the single most responsive gene in embryos exposed to TCDD. TCDD caused strong changes in expression of 12 known genes and at least 21 other genes. In the brain of developing zebrafish, expression in the vasculature was linked to changes in blood flow and apoptosis.