A structural analysis of hepatomegaly induced by a hormone-secreting tumor

Abstract

The hepatic growth observed in rats bearing transplantable hormone (ACTH, growth hormone, prolactin) secreting mammotropic tumors (MtT.F4) has been resolved into three components: (1) an increase in the size of individual parenchymal cells relative to the amount of DNA which they contain; (2) an increase in the DNA contents (ploidies) of the parenchymal cells and of their nuclei; and (3) an increase in the total number of parenchymal cells. As a result of all of these factors, the relative mass of the liver is increased to an extent greater than would have been expected to result from normal growth. Following removal of the tumors there is a reversal of all of these changes, except for a persisting increase in cell number and DNA content, and the resulting cells are smaller than normal. Whereas fatty metamorphosis and other degenerative changes occurred in the latter stages of tumor growth, the initial response was a striking hepatocellular enlargement and proliferation without significant fatty change. Fine structural studies of changes present in livers following 7 weeks of tumor growth showed many enlarged parenchymal cells containing proportional increases in all cytoplasmic constituents. Some cells, generally located at the lobule periphery, were heavily laden with fat vacuoles or showed almost complete fragmentation of the rough endoplasmic reticulum with formation of ribosome-studded vesicles containing material that was apparently secretory in character. Other fine structural changes included an increase in free ribosomes and polysomes and mitochondrial enlargement with the occasional appearance of very large bizarre mitochondrial forms. All changes, except possibly for a slight increase in relative liver mass, were prevented by adrenalectomy of the animal prior to tumor growth.