Objectives of this project are (1) to establish and define a cell culture transformation system for identification of carcinogenic agents and humans at high risk for cancer: (2) to develop human cell transformation systems, with particular emphasis on epithelial cells, in order to study host factors regulating cell transformation and the mechanisms of carcinogenesis by chemicals, viruses, hormones and x-irradiation: and (3) to isolate and characterize oncogenes from human tumors. In line with these objectives, we have (1) established nontumorigenic human bronchial epithelial cell lines infected with simian virus-40 (SV40) or adenovirus-12 (Ad 12)-SV40 hybrid virus, or transfected via strontium phosphate coprecipitation with plasmid containing the SV40 early region genes: (2) demonstrated accelerated malignant conversion of human HBL-100 cells by the v-K-ras oncogene: (3) demonstrated the susceptibility of a human epidermal keratinocyte line to human herpesviruses: (4) demonstrated activation of the met oncogene in an early passage of N-methyl-N'-nitro-N- nitrosoguanidine (MNNG)-transformed human osteosarcoma cells: (5) determined the frequency of active ras oncogenes in human bladder cancers associated with schistosomiasis: (6) demonstrated mutated H-ras oncogenes in human kidney tumors.
