DEVELOPMENT OF CELL LINES EXPRESSING RAT CYTOCHROME

拟议方案具有以下技术目标： (1)大鼠细胞色素P450 NADPH的分离及稳定表达 氧化还原酶cDNA。 (2)评估替代启动子/增强子， 细胞色素P450 cDNA表达。 (3)开发和表征表达大鼠细胞色素的人细胞系 P450 CDNAS。 (4)利用细胞系研究前诱变剂的活化 该计划的总体目标是开发一组细胞系 表达大鼠细胞色素P450 CDNAS。 该小组将赞扬一个 一组表达人细胞色素P450的细胞系， 独立开发。 大多数体内毒理学研究在啮齿动物中进行。 根据啮齿动物毒理学数据估计潜在的人类风险， 困难，因为许多生理差异， 物种 表达人类两种基因的等基因细胞系的可用性 和大鼠细胞色素P450将允许直接，对照比较， 异生物质代谢在观察到的毒理学效应中的作用。 的 进行这些比较的能力有可能提高 跨物种外推的准确性。 SBIR第二阶段研究的产品将是 以两种形式商业化，细胞系将被许可或出售， 商业或非商业用途。 活性酶制剂从这些 细胞，如微粒体，也将出售。我们目前提供类似的 含有人类P450的产品。

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.