Carcinogenicity of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, N-nitrosobis(2-hydroxypropyl)amine and cis-N-nitroso-2,6-dimethylmorpholine administered continuously in the Syrian hamster, and the effect of dietary protein on N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine carcinogenesis.
The effect of continuous week-long administration of the three pancreatic carcinogens N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), N-nitrosobis(2-hydroxypropyl)amine (BHP), and cis-N-nitroso-2,6-dimethylmorpholine (cis-NNDM), by a s.c. implanted osmotic pump, was examined in Syrian hamsters. HPOP at total doses of 220-250 mg/kg body weight induced ductal adenocarcinomas in the pancreas (41%), and cholangiomas (18%) and cholangiocarcinomas (18%) in the liver, 25 weeks following the initiation of treatment. Higher doses of HPOP resulted in severe hepatic injury and increased mortality (LD50 = 280 mg/kg). Cis-NNDM and BHP were less toxic than HPOP and induced pancreatic lesions at doses of 950 mg/kg. These data document that a week-long schedule of continuous administration of HPOP for the induction of pancreatic cancer compares favorably with those involving weekly injections. Application of this model to study the effect of dietary protein in HPOP-induced carcinogenicity showed that the number of cystic, intermediate and tubular complexes in the pancreas was significantly higher in animals fed a 20% as compared to an 8% protein diet 2 weeks prior to HPOP administration. Furthermore, the incidence of pancreatic adenocarcinomas and in situ carcinomas was only 13% in the hamsters fed the low-protein diet as compared to 46% in those fed the high-protein diet.
Kokkinakis
D M
DM
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Scarpelli
D G
DG
D000230:Adenocarcinoma / Q000139:chemically induced; D000818:Animals; D006224:Cricetinae; D004044:Dietary Proteins; D004195:Disease Models, Animal; D008113:Liver Neoplasms / Q000139:chemically induced; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000633:toxicity*; D010190:Pancreatic Neoplasms / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D004044:Dietary Proteins; D009602:Nitrosamines; C014130:N-nitroso-2,6-dimethylmorpholine; C012457:diisopropanolnitrosamine; C013624:N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine