Carcinogenicity of heterocyclic amines for the pancreatic duct epithelium in hamsters

Cancer Lett. 1999 Sep 1;143(2):235-9. doi: 10.1016/s0304-3835(99)00131-7.


Effects of eight heterocyclic amines (HCAs) on pancreatic duct carcinogenesis were investigated in a rapid production model in hamsters. N-Nitrosobis(2-oxopropyl)amine (BOP) was given to effect initiation, followed by augmentation pressure consisting of four daily i.p. injections of 500 mg/kg DL-ethionine, 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 augmentation 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-methylimidazo[4,5-f]quinoline (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9H-pyrido[2,3-b]indole (AalphaC), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) or 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [4,8-DiMeIQx) were administered in the diet for 50 or 70 days. The numbers of pancreatic ductal hyperplasias (H) and a total lesions including, atypical hyperplasia (AH), carcinomas in situ (CIS) and invasive carcinomas, were increased in hamsters given the diet containing 0.02% Trp-P-1 for 50 days. This result was confirmed and extended by the finding of increased numbers of invasive 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 diet containing 0.06% 4,8-DiMeIQx for 50 days. These results suggest a possible involvement of Trp-P-1 and 4,8-DiMeIQx in pancreatic duct carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbolines / toxicity
  • Carcinogens / toxicity*
  • Cricetinae
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Imidazoles / toxicity*
  • Mutagens / toxicity
  • Nitrosamines / toxicity
  • Pancreatic Ducts / drug effects
  • Pancreatic Ducts / pathology*
  • Pancreatic Neoplasms / chemically induced*
  • Pancreatic Neoplasms / pathology
  • Quinoxalines / toxicity*


  • Carbolines
  • Carcinogens
  • Imidazoles
  • Mutagens
  • Nitrosamines
  • Quinoxalines
  • nitrosobis(2-oxopropyl)amine
  • 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole