Pancreatic lesions induced by a single dose of N-nitrosobis(2-oxopropyl)amine and selection by resistance to cytotoxicity

The experiments reported here were undertaken to ascertain whether the principle of the selection and rapid emergence of carcinogen-initiated cells based on their resistance to cytotoxicity demonstrated in rat liver is applicable to hamster pancreas. Hamsters injected with a single dose of 70 mg/kg body weight of the pancreatic carcinogen, N-nitrosobis(2-oxopropyl)amine, were subjected to pancreatic injury and regeneration induced by DL ethionine followed by methionine rescue while on a continuous daily regimen of 10 mg/kg body weight of N-nitroso-2,6-dimethylmorpholine by gavage. Randomly selected animals were killed weekly from the 4th week following the induction of regeneration through the 10th week. This carcinogenic schedule significantly decreased the time of emergence of cell injury, cell death, and proliferative, preneoplastic, and neoplastic lesions of the exocrine pancreas. Carcinoma in situ and invasive adenocarcinoma of pancreatic ducts appeared during the 7th and 8th week after induction of pancreatic regeneration, earlier than results obtained with multiple dose carcinogenesis experiments.