Nitrosamine-induced pancreatic carcinogenesis in outbred and inbred Syrian hamsters.

Abstract

Pancreatic carcinogenesis was investigated in outbred and in five strains of inbred Syrian golden hamsters utilizing the nitrosamines N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP). Thirty eight outbred hamsters were treated for an average of 15 weeks with weekly s.c. inoculations of BHP at doses of 250,000 or 1000 mg/kg. Pancreatic carcinomas developed in 19%. Eighty nine inbred hamsters of strains CB, LHC and PD4 were given BHP at 250 mg/kg weekly for an average of 25 weeks. Pancreatic carcinomas developed in 61%. Pancreatic inflammation, fibrosis, and ductal hyperplasia were prominent. Toxic changes in the liver, biliary hyperplasia, and pulmonary interstitial inflammation were also prominent features of BHP-treated hamsters, along with occasional carcinomas of the liver and respiratory tract. One hundred and sixteen inbred hamsters of strains CB, LHC, LSH, MHA, and PD4 were treated with BOP at a dose of 5 mg/kg weekly for 15 weeks. The incidence of pancreatic carcinoma was 51%. BHP-treated hamsters exhibited pancreatic fibrosis and ductal hyperplasia. Livers of BHP-treated animals showed biliary hyperplasia, and lungs exhibited chronic inflammation. Occasional carcinomas of the liver and lung developed. From 243 hamsters treated with nitroso carcinogens, eight pancreatic ductal adenocarcinoma lines were derived that can be transplanted and propagated in inbred hamsters.