TRANSCRIPTION REGULATORY ELEMENTS IN THE MOUSE CYTOCHROME P-450 GENE

小鼠细胞色素P1450代谢多环芳烃， 特别是致癌物如苯并（a）芘。 这些可以转换为 高活性代谢物则可产生细胞损伤并导致 细胞转化 或者，其他代谢物可以很容易地 与葡萄糖醛酸、谷胱甘肽、SO 4等结合，然后被淘汰 潜在致癌物进入的代谢途径取决于 主要取决于P1450和其他P-450物质、环氧化物 水合酶和结合酶。 为了解 P1450水平可以通过药物和化学物质升高的机制 致癌物，细胞色素P1450基因已被克隆。 整个基因 包括基因帽位点上游1500 bp的序列。 序列 与3-甲基胆蒽的转录调控相关， 2，3，7，8-四氯二苯并对二氧六环（TCDD）的研究 真核表达载体pSV 2-cat和pSV 2-neo。 P1450的DNA 基因，包括RNA聚合酶II启动子区，融合到 CAT基因转染小鼠 hepa-1细胞。 这些细胞具有活性TCDD受体和苯并（a）芘 容易诱导羟化酶活性。 DNA缺失分析和 诱变将用于描绘与以下相关的DNA区域： 受体-配体相互作用和转录激活。

The mouse cytochrome P1450 metabolizes polycyclic aromatic hydrocarbons, particularly carcinogens such as benzo(a)pyrene. These can be converted to highly reactive metabolites then can produce cellular damage and lead to cell transformation. Alternatively, other metabolites can be easily conjugated with glucuronic acid, glutathione, SO4 etc., and eliminated. The metabolic pathways through which a potential carcinogen enters depends largely on the concentration of P1450 and other P-450 species, epoxide hydratase, and conjugating enzymes in the cell. In order to understand the mechanisms by which P1450 levels can be elevated by drugs and chemical carcinogens, the cytochrome P1450 gene has been cloned. The whole gene has been sequenced including 1500 bp upstream of the genes cap site. Sequences associated with transcriptional regulation by 3-methyl-cholanthrene and 2,3,7,8 tetrachlorodibenzo-p-dioxane (TCDD) are being studied by use of the eukaryote expression vectors, pSV2-cat and pSV2-neo. DNA from the P1450 gene, including the RNA polymerase II promoter region, is fused to the choloramphenical acetyltransferase gene (CAT) and transfected into mouse hepa-1 cells. These cells have an active TCDD receptor and benzo(a)pyrene hydroxylase activity is readily induced. DNA deletion analysis and mutagenesis will be used to delineate regions of DNA associated with receptor-ligand interactions and transcriptional activation.