A light and electron microscopic study of liver and lung tumors induced by a single low dose of diethylnitrosamine (DEN) in C57BLXC3H F1 mice.

The effect of a single intragastric dose of DEN was studied in 15-day-old male C57BLXC3H F1 mice. Group 1 was given 0.315, group 2, 0.625 micrograms/g, and group 3 served as a vehicle control. Animals were sacrificed at regular intervals up to 75 weeks. Liver and lung tissue were examined by light and electron microscopy. Mice of group 1 and 2 developed liver lesions ranging from hyperplastic nodules to hepatocellular adenomas and carcinomas. The incidence of these lesions varied with the length of observation period. Electron-dense crystalline inclusions of alpha 1 antitrypsin were found in the dilated cisternae of the rough endoplasmic reticulum of the hyperplastic and adenomatous nodules. The incidence of lung adenomas was significantly higher in group 3 than groups 1 and 2; ultrastructurally these tumors contained both Clara cells and type II pneumocytes. The results indicate that DEN is effective even in a low single dose in inducing liver and lung tumors in mice.