Experimental induction of pancreatic carcinomas in the hamster with N delta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine.

Carcinomas of the pancreas, stomach, and breast, as well as mesotheliomas and ovarian stromal tumors, were induced in Syrian golden hamsters treated with N delta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO), which has previously been shown to cause pancreatic acinar cell carcinomas in rats. The pancreatic carcinomas in hamsters appeared ductlike. The nonneoplastic and preneoplastic lesions induced in the hamster pancreas included cystic ductal complexes, tubular complexes, intraductal hyperplasia and atypical hyperplasia, focal eosinophilic metaplasia, and foci of atypical acinar cells. High doses of 654 mg MNCO/kg body weight were cytotoxic for acinar cells and caused atrophy of the pancreas. Alkaline elution analysis of DNA from acinar cells treated in culture with MNCO showed an increased rate of elution characteristic of single-strand breaks. A group of hamsters treated with a low dose of N-nitrosobis(2-oxopropyl)amine (BOP) developed pancreatic lesions similar to those seen when a subcarcinogenic dose of MNCO was given. The results suggest that MNCO affects both acinar and ductal cells in the hamster and that the response of the hamster pancreas to MNCO and BOP is similar in many respects.