N-Nitroso-2,6-dimethylmorpholine-Induced Hemangiosarcomas in the Livers of Randombred Guinea Pigs2

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Abstract
The carcinogenic effect of N-nitroso-2,6-dimethylmorpholine (DMNM) was studied in randombred guinea pigs after repeated administration of this compound by gavage. DMNM was administered at two dose levels (14 and 28 mg/kg body wt) weekly for 23 weeks. All animals were observed until their death or termination of the experiment at 54 and 37 weeks for the 14- and 28-mg dose levels, respectively. At 14 mg, 67% of the animals developed hemangiosarcomas of the liver and 60% developed cholangiomas between 36 and 54 weeks. In addition, a poorly differentiated malignant mesenchymal tumor was observed in 1 animal. At 28 mg, liver hemangiosarcomas were observed in 82% of the animals between 26 and 37 weeks. In addition, in 18% of the animals, bronchioalveolar adenoma (1 animal), hepatocellular carcinoma (1 animal), and malignant lymphoma (1 animal) were also induced. Metastases of hemangiosarcomas to lungs, mesenteries, and lymph nodes were observed in 3 animals of each group.