The proposed program has the following technical objectives: (1) Isolate and obtain stable expression of a rat cytochrome P450 NADPH oxido-reductase CDNA. (2) Evaluate alternative promoters/enhancers for more efficient cytochrome P450 CDNA expression. (3) Develop and characterize human cell lines expressing rat cytochrome P450 CDNAS. (4) Utilize the cell lines to study activation of promutagens The overall goal of this program is to develop a panel of cell lines expressing rat cytochrome P450 CDNAS. This panel will compliment a panel of cell lines expressing human cytochrome P450s which is being developed independently. The majority of in vivo toxicology studies are performed in rodents. Estimation of potential human risk from rodent toxicology data has been difficult because of the many physiological differences between the species. The availability of isogenic cell lines expressing both human and rat cytochrome P450s will allow direct, controlled comparison of the role of xenobiotic metabolism in observed toxicological effects. The ability to perform these comparisons has the potential to improve the accuaracy of across species extrapolations. The products resulting from this SBIR phase II research will be commercialized in two forms, The cell lines will be licensed or sold for commercial or non-commercial use. Active enzyme preparations from these cells, such as microsomes, will also be sold. We currently offer similar products which contain human P450s.
