Chemopreventive effects on carcinogenesis in a hamster model (CDDB model) *
[Background] The effects of chemoperventive agents on carcinogenesis were examined using a hamster model (cholecystoduodenostomy with dissection of the extrahepatic bile duct at the distal end of the common duct [CDDB] model ) initiated with N-Nitrosobis (2-oxopropyl) amine (BOP). It is recognized that the CDDB model replicates pancreaticobiliary maljunction in man. [Material and method] Seven-week old Syrian golden hamsters were operated on for the CDDB model. Four weeks after CDDB, all the animals were subcutaneously injected with BOP (10 mg/kg) weekly for six weeks . The animals were divided into six groups ; group 1 received drinking water throughout the experimental period, group 2 received cimetidine throughout the experimental period, group 3 received FOY-305 throughout the experimental period, group 4 received ranitidine throughout the experimental period, group 5 received etodolac throughout the experimental period, and group 6 received MGN-3 throughout the experimental period. [Results] The mean number of carcinomas and total lesions in the pancreas, atypical hyperplasia lesions in the extrahepatic bile duct, atypical hyperplasia and carcinoma lesions in the intrahepatic bile duct, and atypical hyperplasia and total lesions in the gallbladder in the etodolac group were significantly less than those in the no therapy group. The mean number of hyperplasia and total lesions in the pancreas, atypical hyperplasia and total lesions in the extrahepatic bile duct, and total lesions in the gallbladder in the cimetidine group were significantly less than those in the no therapy group. The mean number of hyperplasia lesions in the pancreas in the ranitidine group was significantly less than that in the no therapy group, but no difference in other lesions was observed. The mean number of hyperplasia and total lesions in the pancreas, atypical hyperplasia and total lesions in the extrahepatic bile duct, atypical hyperplasia lesions in the intrahepatic bile duct, and atypical hyperplasia and total lesions in the gallbladder in the FOY-305 group was significantly less than those in no therapy group. The mean number of hyperplasia lesions in the gallbladder in the MGN-3 group was significantly less than that in the no therapy group. There was not a difference in the mean number of total lesions in the intrahepatic bile duct, but the mean number of hyperplasia lesions in the MGN-3 group was significantly higher than that in the no therapy group. [Discussion and conclusion] These results suggest that etodolac, which has the inhibitory effects of a cyclooxygenase-2, has chemopreventive potential in the CDDB model. Cimetidine and ranitidine are histamine type-2 receptor antagonists. The main chemopreventive effect of cimetidine might be its inhibitory effects on E-setectoin. It does not influence the quantity of reflux of duodenal contents into the biliary tract. The serine protease inhibitor FOY-305 inhibited lesion development. This is probably because this CDDB model affects the activity of the pancreatic enzyme. Etodolac, cimetidine and FoY-305 can be administered orally and no side effects were seen. These results suggest that these agents escapes from MGN-3 have a chemopreventive potential in the CDDB model. (Accepted on September 27, 2002) Kawasaki Igakkaishi 28(4 ) : 257-268, 2002
