PHENOTYPING OF HUMAN CYTOCHROME P-450

人细胞色素 P-450 的表型分析

• 批准号: 3916767
• 负责人: F K FRIEDMAN
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916767
• 关键词: chemical carcinogenesis; cytochrome P450; drug interactions; enzyme mechanism; enzyme substrate; ethanol; human tissue; isozymes; laboratory mouse; laboratory rat; liver metabolism; microsomes; monoclonal antibody; nitrosamines; protein sequence; radioimmunoassay; toxin metabolism

The individual forms of cytochrome P-450 display unique substrate specificity and reactivity profiles toward a variety of drugs and carcinogens. Differences in cytochrome P-450 phenotype may relate to individual differences in sensitivity to certain drugs and susceptibility to chemical carcinogenesis. Monoclonal antibodies (MAbs) to various forms of rat liver cytochrome P-450 have been used as specific probes for the cytochrome P-450s in human liver. Western blot analysis with MAb to rat ethanol-induced P-450, a form with high nitrosamine metabolizing activity, detected a related P- 450 in human liver microsomes. Individual variation in the level of this P-450 was observed. A radioimmunoassay (RIA) to this P- 450 was developed with MAb 1-98-1. Using this assay we were able to detect and quantitate the MAb-specific cytochrome P-450 in human liver microsomes. This human P-450 was immunopurified and analyzed by peptide maps and amino acid sequencing.

细胞色素P-450的不同形式显示出独特的底物 对多种药物的特异性和反应性特征， 致癌物质。 细胞色素P-450表型的差异可能与 对某些药物敏感性的个体差异， 对化学致癌作用的敏感性。 单克隆抗体 （单克隆抗体）的各种形式的大鼠肝细胞色素P-450已被 用作人肝细胞色素P-450的特异性探针。 用单克隆抗体对大鼠乙醇诱导的P-450的蛋白质印迹分析， 具有较高的亚硝胺代谢活性，检测到相关的P- 450人肝微粒体。 水平的个体差异 P-450被发现 用放射免疫分析法（RIA）测定了该P- 450用MAb 1-98-1开发。 利用这种分析，我们能够 检测和定量人血清中MAb特异性细胞色素P-450 肝微粒体 将该人P-450免疫纯化并分析 通过肽图谱和氨基酸测序。