Metaplastic pancreatic cells in liver tumors induced by diethylnitrosamine

Metaplastic pancreatic cells have been infrequently observed in fish liver tumors induced by chemical carcinogens. An investigation with nitrosamine-exposed trout was undertaken to characterize the relationships of metaplastic pancreatic cells with other cell types. Eight-week-old rainbow trout (Salmo gairdneri) were fed a control diet or diets containing 500 ppm beta-naphthoflavone (BNF), 2000 ppm indole-3-carbinol (13C), or 100 ppm Aroclor 1254 (PCB) for 6 weeks. The fish were then exposed to 250 ppm diethylnitrosamine for 24 hr in an aqueous aquarium bath and reared on control diet for 39 weeks postexposure. Livers were excised, processed to paraffin sections, and stained with hematoxylin and eosin for histological evaluation. Metaplastic pancreatic cells were found only in tumors. Of the tumors with metaplastic pancreatic cells, 100/105 (95.2%) contained neoplastic cholangiolar components. Only 5/105 (4.76%) were hepatocellular carcinomas. 13C pretreatment inhibited the incidence of cholangiolar tumors (cholangioma 3.6% vs 31.3%, cholangiocarcinoma 3.6% vs 13.0%) and metaplastic pancreatic cells (5.1% vs 19.1%), whereas BNF and PCB had no effect. A hepatocellular origin for metaplastic pancreatic cells is supported. Cholangiolar neoplasia is associated with the expression, growth, or survival of metaplastic pancreatic cells in liver tumors. Hepatocarcinogenicity should not be described entirely by hepatocellular events since cholangiolar and metaplastic pancreatic cells can respond associatively to carcinogens and dietary modulators.