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.
