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

多环芳烃诱导氧化酶和共轭酶 在反应灵敏的动物和人类细胞中。氧化酶，即， 细胞色素P-450，从前致癌物产生活性中间体 从而引发化学致癌。我们建议对此进行调查 直接引入分子克隆全长P-450的假说 CDNA进入不同的细胞，并分析结合的程度 致癌物对细胞大分子的作用，并通过 用合适的致癌物来挑战。 为此，我们计划使用感染性真核表达 载体，痘苗病毒，以前被证明是以酶的方式表达的 被运输到适当的亚细胞的活性外源蛋白 居住地点。我们已经将小鼠P1-450和P3-450引入 重组载体，并正在将它们转移到 产生具有感染性的重组痘苗病毒。

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.