Molecular Aspects during Multi-step Chemical Induced Carcinogenesis in the Lung and Pancreas

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Alterations of various genes during N-nitrosobis(2-hydroxypropyl)amine (BHP) -induced lung carcinogenesis in rats and N-nitrosobis(2-oxopropyl)amine (BOP) -induced pancreatic duct carinogenesis in hamsters were summarized. In both carinogenesis, Ki-ras mutation was the early event in lung alveolar and pancreatic duct hyperplasias. Although p53 mutation was not detected in lung adenocarcinomas, it was revealed as late events in transplantable pancreatic carcinoma and its cell lines. FHIT alterations were found in rat lung adenocarcinomas and in hamster pancreatic duct carcinomas. The induced lesions in both rat lung and hamster pancreas were histologically and genetically similar to those seen in humans. It was evident from this study that various gene alterations were accumulated from preneoplastic lesions to carcinomas induced by nitrosoamines in rat lung and hamster pancreas. Since cancer is a disease of gene alterations, the detection of genetic and environmental factors which induce organ specific gene alterations is important for the prevention and early detection and treatment of lung and pancreatic cancers.
2003-09-30