Preneoplastic steps such as metaplasia, hyperplasia, and atypia are considered pathological steps in the development human carcinoma. Multiphasic oncogene activation during carcinogenesis is shown to occur in malignant neoplasia. Oncogene activation is usually determined by morphological transformation of NIH3T3 cells. It is proposed to demonstrate the activation of oncogenes in tumors induced in human pancreas explants, to determine and compare the temporal relationship between the activation of the oncogene and morphological steps in pancreas carcinogenesis. It is further proposed to develop a system for detection of oncogene activation other than NIH3T3 cells. This model will be based on the morphological transformation of human pancreas cell lines in vitro and their tumorigenicity in "athymic nude" mice in vivo.