This project is to assess the role of viruses in the multistage process of human lung carcinogenesis, using normal bronchial epithelial and mesothelial cells. Immortalized, nontumorigenic clonal cell lines have been derived from these cell types via viral infection (SV40 virus, BK virus, or adenovirus-12--SV40 hybrid virus) or transfection of viral genes (SV40 T-antigen gene-, or SV40 genome-containing plasmids). Some of the bronchial epithelial cell lines retain the ability to undergo terminal squamous differentiation in response to serum. These cells are being used for studies of the effects of other DNA tumor virus genes, other oncogenes, and carcinogens.