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Ultrastructure of Spontaneous Hyperplastic Nodules in Mouse Liver¹

Division of Cytology, Sloan-Kettering Institute for Cancer Research, and the Sloan-Kettering Division, Cornell University Medical College, New York, New York

The fine structure of parenchymatous cells in a series of spontaneous, hyperplastic nodules in aging C3H mice is described. These nodules were circumscribed, frequently lacked central and portal veins, and sometimes exhibited a variety of other changes including hydropic vacuolization, fatty infiltration, and dilation of sinusoids. The nuclei of the parenchymatous cells were smaller and more uniform in size while the cytoplasm was more basophilic and often vacuolated. All the nodules showed varying degrees of alteration in fine structure particularly in the Golgi apparatus and mitochondria. Most striking, however, were alterations in the rough endoplasmic reticulum in which the normally flattened cisternae were transformed into either a dilated or a tubular form, containing amorphous, granular, or filamentous material. The filaments measured about 33 mµ in diameter. Of interest is the fact that similar changes in the endoplasmic reticulum were also observed in an apparently "normal" liver from a mouse of the same age group. The nature of the histologic changes in the hyperplastic nodules are considered. The significance of the various altered forms of endoplasmic reticulum and their unusual contents in parenchymatous cells of both hyperplastic nodules and "normal" liver are discussed. The question whether these changes as well as alterations in other cell organelles are the result of unfavorable environmental conditions in the growing nodule is also considered.

¹ This investigation was supported by Contract U-1096 II C4 from the Health Research Council of the City of New York, by Grant E406 from the American Cancer Society and in part by NCI Grant CA-08748.

Received 1/25/67. Accepted 7/ 5/67.