Dimethylnitrosamine-induced Hepatic Cell Carcinoma in Rainbow Trout

SUMMARY-Liver neoplasms (adenomas and adenocarcinomas) were induced in rainbow trout by feeding dimethylnitrosamine [(DMN) N-nitrosodimethylamine] at levels ranging from 7.5-1920 mg/1 00 g dry test diet for 9 months or longer. Neoplasms were grossly and histologically similar to those reported by various authors for rats and other mammals. Hemorrhagic ascites, commonly observed in hepatomatous mammals, was largely absent from hepatomatous DMN-fed trout. Metastases seldom occurred in these trout within the 20-month period of the experiments, but direct spread of neoplasms from liver to visceral fascia and to pancreatic adipose tissue sometimes occurred. Extensive proliferation of bile ducts or ductules was rare in DMN-fed trout in contrast to prevalence of such pro-liferations in several species of DMN-fed mammals. Cystic areas in some of the trout neoplasms appeared to arise from acinous-like formations not related to bile-duct proliferations. Central necrosis and hemorrhage in the larger neoplasms usually spread peripherally until most of the primary neoplastic tissue was destroyed. Control fish fed the complete test diet for similar periods had none of the above pathological anomalies.-J Nat Cancer Inst 41: 531-552, 1968_ THIS PAPER records the appearance of a high incidence of liver cell neoplasms in rainbow trout fed dimethylnitrosamine [(DMN) N-nitrosodi-methylamine] in the diet for 20 months. These experiments grew out of a nationwide epizootic of rainbow trout hepatoma first recognized in 1960 (1, 2). Experiments were started late in 1960 at this laboratory to determine the response of rainbow trout to 13 classes of chemical carcinogens added to a complete test diet. All but 1 of 13 chemicals tested induced some liver neoplasms, depending on the level and type of carcinogen ingested. DMN proved a potent carcinogen in these preliminary screening experiments at the levels used in the diet