The goals 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; (3) to isolate and characterize oncogenes from human or primate tumors; and (4) to develop and test measures to prevent and/or control cell transformation and the neoplastic event for eventual clinical application. Major findings were: (1) establishment of a nontumorigenic human epidermal keratinocyte line immortalized by exposure to Ad 12-SV40 virus; (2) malignant transformation of human epidermal keratinocytes by the combined action of Ad 12-SV40 virus and Ki-MSV; (3) neoplastic conversion of human keratinocytes by Ad 12-SV40 virus and chemical carcinogens (MNNG or 4NQO), which should be useful in assessing environmental carcinogens and detecting new human oncogenes; (4) keratin expression of tumorigenic chemically and virally transformed human epidermal cells was similar to that of control cells; (5) thyroid hormone optimized transformation by Ki-MSV; (6) hydrocortisone enhanced expression of Epstein-Barr virus (EBV) genomes in human cells; (7) Ha-ras was found to be activated in about 10% of human urinary tract tumors; (8) an N-ras gene was detected in 7060 human rectal carcinoma-derived cells, as well as a restriction fragment length polymorphism of human c-myb gene.
