Carcinogenicity of heterocyclic amines for the pancreatic duct epithelium in hamsters.
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.
Yoshimoto
M
M
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Tsutsumi
M
M
Iki
K
K
Sasaki
Y
Y
Tsujiuchi
T
T
Sugimura
T
T
Wakabayashi
K
K
Konishi
Y
Y
D000818:Animals; D002243:Carbolines / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D007093:Imidazoles / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity; D009602:Nitrosamines / Q000633:toxicity; D010183:Pancreatic Ducts / Q000187:drug effects / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D011810:Quinoxalines / Q000633:toxicity*
D002243:Carbolines; D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; D009602:Nitrosamines; D011810:Quinoxalines; C013622:nitrosobis(2-oxopropyl)amine; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole