ハムスターにおける膵細胞増殖能を指標とした膵発癌物質の検索

Abstract

Since a high incidence of pancreatic ductal carcinomas can be obtained within only 10 weeks by repeated "augmentation pressure" treatment in a rapid production model for hamsters, chemically initiated cell populations are believed to have proliferative advantage. Based on this hypothesis, I studied the 5-bromo-deoxyuridine (BrdU) labeling index (LI), as an indicator of cell proliferation during "augmentation pressure". I also studied the effects of several non-pancreatic carcinogens on cell proliferation in this experimental system to screen their possible contribution to pancreatic carcinogenesis. The results were as follows : 1) In control groups without initiation, LI of pancreatic ductal cells increased slightly during augmentation pressure, with a peak being observed 16 days after the study com- mencement. 2) Among pancreatic ductal carcinogens in hamsters, carcinogenic doses of both N- nitrosobis(2-oxopropyl)amine or N-nitrosobis(2-hydroxypropyl)-amine clearly amplified the increase of LI in main pancreatic duct cells. However, N-methyl-N-nitrosourea, administered below a carcinogenic dose, had no effect. 3) Both azaserine and 4-hydroxyaminoquinoline, pancreatic acinar cell carcinogens, also amplified the increase of LI in main duct cells. 4) Among non-pancreatic carcinogens, diethylnitrosamine, dimethylnitrosamine, and 3- amino-1, 4-dimethyl-5H-pyrido(4, 3-b)indole amplified the increase of LI in main duct cells, while N-methyl-N-nitroso-N'-nitrosoguanidine and benzo(a)pyrene had no effect. These results suggest that initiated cell populations selectively proliferate during "augmentation pressure" and that quantification of cell proliferation under this experimental system is a useful marker to detect pancreatic ductal carcinogens within a short period. Also our data show possible risk of several carcinogens regarding pancreatic ductal neoplasia through increasing proliferation of target cell populations.