Ultrastructural features of diethylnitrosamine-induced lesions in the mouse liver.

Mice were given a single dose of diethylnitrosamine (DEN). After 12 and 15 months, the ultrastructural features of simple hepatic nodules and defined hepatocellular carcinomas were compared. The main difference between these two lesions is the presence of highly convoluted membranes in the hepatocytes of the carcinomas. A third population of nodules was also found which could not be easily classified at the light microscope level into either simple hepatic nodules or carcinomas. Ultrastructural examination of these lesions showed them to have areas resembling both simple hepatic nodules and carcinomas. Within both these areas hepatocytes with convoluted plasma membranes were observed. Changes in membrane pattern may be indicative of an altered cell growth pattern and the acquisition of invasive or metastatic properties. This provides further evidence suggesting that a sub-population of cells can be identified which has the potential to develop into overt carcinoma.