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.
