Carcinogenicity of heterocyclic amines for the pancreatic duct epithelium in hamsters

Effects of eight heterocyclic amines (HCAs) on pancreatic duct carcinogenes is were investigated in a rapid production model in hamsters. N-Nitrosobis( 2-oxopropyl)amine (BOP) was given to effect initiation,followed by augmenta tion pressure consisting of four daily i.p. injections of 500 mg/kg DL-ethi onine, a choline-deficient (CD) diet, a single i.p. injection of 800 mg/kg L-methionine and a s.c. injection of 20 mg/kg BOP. After two cycles of augm entation pressure, the HCAs 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-m ethylimidazo[4,5-f]quinoline (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]ind ole (Trp-P-1), 3-amino-1-methyl-SH-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9 H-pyrido[2,3-b]indole (A alpha C), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) or 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [4,8-DiMe IQx) were administered in the diet for 50 or 70 days. The numbers of pancre atic ductal hyperplasias (H) and a total lesions including, atypical hyperp lasia (AH), carcinomas in situ (CIS) and invasive carcinomas, were increase d in hamsters given the diet containing 0.02% Trp-P-1 for 50 days. This res ult was confirmed and extended by the finding of increased numbers of invas ive carcinomas in hamsters given 0.02% Trp-P-1 for 70 days. The number and incidence of invasive carcinomas were also elevated in hamsters given the d iet containing 0.06% 4,8-DiMeIQx for 50 days. These results suggest a possi ble involvement of Trp-P-1 and 4,8-DiMeIQx in pancreatic duct carcinogenesi s. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.