methylazoxymethanol and Pancreatic-Neoplasms

To determine if hyperplastic and neoplastic lesions from medaka showed similar immunoreactivity to intermediate filament antibodies as the tissues of origin, two week old medaka were exposed to 10 or 20 mg/L of methylazoxymethanol acetate for two hours and transferred to clean water for up to six months. Using a streptavidin peroxidase method, paraffin embedded Bouins fixed neoplasms were incubated with cytokeratin, vimentin, or neurofilament antibodies. Like their nonneoplastic cellular counterparts, hepatocellular carcinoma, pancreatic acinar carcinoma and mesenchymal neoplasms including hemangioma and hemangiopericytoma reacted negatively to cytokeratin antibodies. Cholangiocarcinoma, mesothelioma, and proliferative lesions containing biliary epithelial cells reacted positively to cytokeratin antibodies. All neoplasms and proliferative lesions were negative with vimentin and neurofilament antibodies. These data indicate that while some epithelial neoplasms showed cytokeratin reactivity similar to the parent tissues, additional markers are needed to identify mesenchymal tissues and neoplasms.

Topics: Adenoma, Liver Cell; Animals; Antibodies; Carcinogens; Carcinoma, Acinar Cell; Carcinoma, Hepatocellular; Cell Division; Cholangiocarcinoma; Hemangioma; Hemangiopericytoma; Hyperplasia; Immunohistochemistry; Intermediate Filaments; Keratins; Liver; Liver Neoplasms; Methylazoxymethanol Acetate; Neurofilament Proteins; Oryzias; Pancreas; Pancreatic Neoplasms; Vimentin

Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following a single brief exposure to methylazoxymethanol acetate [(MAM-Ac) CAS: 592-62-1]. Fish 6-10 days old were exposed to concentrations of MAM-Ac up to 100 mg/liter for 2 hours. Exposed specimens were transferred to carcinogen-free water and sampled periodically for tumor development. Pancreatic neoplasms occurred in approximately 9% of histologically examined individuals exposed to 10 mg MAM-Ac/liter or less. Neoplastic lesions were not found in 122 control specimens. The neoplasms included 6 cases diagnosed as adenoma, 7 cases diagnosed as acinar cell carcinoma, and 2 cases diagnosed as adenocarcinoma. Adenomas consisted mainly of well-differentiated acinar cells that were filled with zymogen granules. Two adenomas also contained foci of atypical, less-differentiated acinar cells possessing basophilic, fibrillar cytoplasm. Acinar cell carcinomas occurred in several cellular patterns that ranged from well-differentiated to more anaplastic lesions; however, none exhibited areas of ductular proliferation. Adenocarcinomas, on the other hand, exhibited a glandular growth pattern and contained numerous ductlike structures. Both types of carcinomas appear to arise from primary acinar cells. Thus lesions probably progress from adenomas to acinar cell carcinomas and adenocarcinomas. The findings of carcinogen-induced pancreatic neoplasms in guppies further strengthen the usefulness of small fish species in carcinogen testing and provide an additional model for pancreatic tumors.

Topics: Adenocarcinoma; Adenoma; Animals; Azo Compounds; Methylazoxymethanol Acetate; Pancreas; Pancreatic Neoplasms; Poecilia