THE ROLE OF MOUSE CYTOCHROME P1-450 AND P3-450 IN CARCINOGENESIS

小鼠细胞色素 P1-450 和 P3-450 在致癌作用中的作用

• 批准号: 4692456
• 负责人: N BATTULA
• 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/4692456
• 关键词: chemical carcinogen; chemical carcinogenesis; complementary DNA; cytochrome P450; enzyme induction /repression; eukaryote; genetic manipulation; genetic recombination; macromolecule; molecular cloning; vaccinia virus

Polycyclic aromatic hydrocarbons induce oxidative and conjugative enzymes in responsive animals and in human cells. The oxidative enzymes, i.e., cytochrome P-450s, generate active intermediates from procarcinogens and thus initiate chemical carcinogenesis. We propose to investigate this hypothesis by directly introducing molecularly cloned full length P-450 cDNAs into different cells and analyzing the extent of binding of the carcinogen to the cellular macromolecules, and the incidence of tumors by challenging with appropriate carcinogens. For this purpose, we plan to use the infectious eukaryotic expression vector, vaccinia virus, which was previously shown to express enzymatically active foreign proteins that are transported to the appropriate subcellular site of residence. We have introduced the mouse P1-450 and P3-450 into the recomination vector and are in the process of transferring these into the vaccinia virus to generate the infectious recombinant vaccinia virus.

多环芳烃诱导氧化酶和结合酶 在有反应的动物和人类细胞中。 氧化酶，即， 细胞色素P-450，从原致癌物产生活性中间体， 从而引发化学致癌作用。 我们建议对此进行调查 通过直接引入分子克隆的全长P-450 将cDNA导入不同的细胞中，并分析这些cDNA的结合程度。 致癌物质的细胞大分子，和肿瘤的发病率， 用适当的致癌物质来挑战。 为此，我们计划使用感染性真核表达 载体，牛痘病毒，其先前显示酶促表达 活性外源蛋白被转运到适当的亚细胞 居住地。 我们已经将鼠标P1-450和P3-450引入到 重组载体，并正在将这些转移到 所述方法包括将所述重组牛痘病毒接种至所述感染性重组牛痘病毒以产生所述感染性重组牛痘病毒。