NEOPLASTIC AND PRENEOPLASTIC LESIONS IN RATS AFTER ORAL-ADMINISTRATION OF A SINGLE DOSE OF N-NITROSOMORPHOLINE

The administration of a single oral dose of 320 mg/kg body wt. N-nitrosomorpholine (NNM) to 62 Sprague-Dawley rats resulted in neoplastic and preneoplastic changes in different organs, especially in liver and kidney. After a lag period of 4 weeks, nearly all experimental animals developed preneoplastic (clear cell, acidophilic, basophilic, mixed cell) foci of the liver parenchyma. Sporadically, small neoplastic nodules were found in the liver as early as 4 weeks after the beginning of the experiment. After a lag period of 1-2 years, 4 of 13 rats showed multiple neoplastic hepatic nodules and one animal a hepatocellular carcinoma. The bile ductules of some animals responded to the carcinogen by forming mocous cholangiofibroses and cystic cholangiomas. After long lag periods, large cholangiofibromas were found in two experimental animals. One or two years after application of the carcinogen, many animals developed epithelial (clear cell, acidophilic, chromophobic, basophilic, oncocytic) kidney tumors, often cystic. Pathologically changed (clear cell, chromophobic, basophilic, oncocytic) tubules are regarded as precursors of the epithelial tumors. The altered tubules appear for the first time at about half a year after application of the carcinogen. Apart from multiple cysts of the liver and kidneys some pancreatic cysts developed in two animals. In addition, two mesenchymal kidney tumors, one malignant neurinoma, two subcutaneous fibromas, one fibroadenoma, and one squamous cell carcinoma of the skin were observed. © 1979 Springer-Verlag.