NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS BY ONCOGENES OR CARCINOGENS

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Five families of activated protooncogenes, ras, raf, jun, erbB-2 (neu) and myc have so far been associated with human bronchogenic carcinoma. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumor progression. The oncogene-transformed cells contained abnormal patterns of DNA methylation that were similar to those found in primary lung cancers. Since the major cause of bronchogenic carcinoma is tobacco smoke, continuing investigations have recently shown that benzo[a]pyrene or 1,6- dinitropyrene will cause neoplastic transformation of human bronchial epithelial cells. The transformed cells form metastatic adenocarcinomas in athymic nude mice. This new in vivo/in vitro model of tobacco carcino- genesis should lead to new mechanistic insights and opportunities for intervention and chemoprevention. An in vitro model of human hepatocellular carcinogenesis is being developed. SV40 T immortalized human hepatocytes have been shown to metabolically activate carcinogens including aflatoxin B1 from 3 different chemical classes.