Mechanistic analysis of pancreatic ductal carcinogenesis from pancreatic juice – Mutagenicity of pancreatic juice in animals treated with carcinogens – *
Pancreatic duct adenocarcinoma has one of the lowest cure rates of all human malignancies. Therefore, the development of chemopreventive methods to inhibit or delay carcinogenesis and progression of cancer extremely important. Pancreatic duct adenocarcinoma originates in the ductal epithelium of the pancreas. The secretion of carcinogens into pancreatic juice is considered to be an important factor in carcinogenesis of the pancreatic duct, because the ductal epithelium of the pancreas is exposed to pancreatic juice. However, little is known about the role of pancreatic juice in carcinogenesis of the pancreatic duct. Nitrosamines such as BOP and BHP have been found to initiate pancreatic duct adenocarcinoma in hamsters, but not in rats. In the present study, we examined the mutagenicities and mutagens of pancreatic juice collected after administration of nitrosamines using Ames test and HPLC. The pancreatic juice obtained from hamsters treated with BOP and BHP showed high mutagenicities and the metabolism of BOP and BHP was detected, that obtained from rats, however, did not. These results suggest that the secretion of carcinogens into pancreatic juice plays an important role in carcinogenesis of the pancreatic duct, and that the Ames test using pancreatic juice could prove useful as a screening method for carcinogens of the pancreatic duct.(Accepted on October 24，2005)
