TOXI 7 |
| Oxidative metabolism by cytochromes P450 (CYPs) can determine the biological activity, toxicity and half-life of many of drugs, carcinogens and other toxicants. We study the evolutionary, regulatory and functional relationships among CYPs, currently focusing on zebrafish. Zebrafish have 90 CYP genes, 55 in gene families 1-4 that are responsible for xenobiotic metabolism; three CYP3s, six CYP4s, and 41 CYP2s in 11 subfamilies, which are poorly known. Zebrafish have five CYP1s; CYP1A, 1B1, 1C1 and 1C2 are inducible by aryl hydrocarbon receptor agonists, while CYP1D1 is under constitutive control. The CYP1s show organ, cell and developmental stage differences in expression. CYP1A is prominently induced in the endothelium, and appears to contribute to oxidative stress in embryos. Chemical regulation of zebrafish CYPs is being addressed with a zebrafish CYP/nuclear receptor microarray. Substrates are known for few zebrafish CYP. Modeling and docking studies are revealing potential substrates and differences between orthologues. (NIH 5-P42-ES0-07381)
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Zebrafish in Drug Development and Chemical Toxicology
2:00 PM-4:40 PM, Sunday, August 19, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |