CLONING AND CHARACTERIZATION OF HUMAN CYTOCHROME P-450

正在使用免疫化学方法分离人细胞色素P-450 基因。细胞色素P-450从大鼠肝脏中纯化并广泛应用 以外源物质和类固醇的诱导性为特征，以及 催化活性。然后生产兔抗细胞色素P-450，并 用于筛选人cdna表达文库。全长cDNA是 并测定了它们的序列。将这些cDNA与 它们的啮齿动物P-450的对应物。经过充分的表征，P-450 将使用cDNA探针来分析细胞色素P-450在细胞中的调节 培养的人类细胞和淋巴细胞。此外，这些探测器将被 用来研究人类的遗传差异。作为一个模范系统，我们将 首次尝试鉴定人类脱氢异喹的编码基因 4-羟基酶。这种酶系统在人类中的多态性一直是 有据可查。

Immunochemical methods are being employed to isolate human cytochrome P-450 genes. Cytochrome P-450s are purified from rat liver and extensively characterized with regard to inducivility by xenobiotics and steroids, and catalytic activity. Rabbit anti-cytochrome P-450 is then produced and utilized to screen human cDNA expression libraries. Full length cDNAs are isolated and their sequences are determined. These cDNAs are compared with their rodent P-450 counterparts. After sufficient characterization, P-450 cDNA probes will be used to analyze the regulation of cytochrome P-450 in cultured human cells and lymphocytes. In addition, these probes will be utilized to examine human genetic differences. As a model system we will first attempt to characterize the gene coding for the human debrisoquine 4-hydroxylase. The polymorphism of this enzyme system in humans has been well documented.