ENZYMATIC HISTOCHEMISTRY OF ETHIONINE INDUCED LIVER CIRRHOSIS AND HEPATOMA

A number of enzymatic histochemical staining reactions were applied to the livers of rats that had been given dl-ethionine for periods up to 330 days. The ethionine lesion is characterized by early central hepatocellular necrosis, proliferation of oval cells, and degenerative and regenerative alterations in the liver cells leading to cirrhosis and areas of adenofibrosis. Finally, liver cell carcinoma develops. The zonal differences of various enzymatic staining reactions in the liver lobules characteristic for the normal liver disappear in regenerating liver lobules. Most enzymes are demonstrable in these regenerating cells, as for instance succinic dehydrogenase, nonspecific esterase, glucose-6-phosphatase, diphosphopyridine nucleotide diaphorase and others. Hepatic carcinoma cells likewise retain many of the staining reactions. There is, however, a complete lack of bile canalicular activity, which is best seen with the ATPase technique. Such a deficiency occurs also in some regenerating nodules without obvious evidence of malignancy. Thus, the lack of bile canalicular staining in cirrhotic liver lobules may indicate impending carcinomatous transformation. Oval "ductular" cells showed a lack of various enzymatic staining reactions, but did show moderate DPN diaphorase and nonspecific esterase activity. The origin of these cells from liver cells, although not proven, is definitely suggested. In areas of oval cell proliferation, there was marked increase in the intensity of sinusoidal staining with various phosphatase techniques. Fibrous tissue, particularly in areas of adenofibrosis, showed areas of marked adenosine triphosphatase activity. On the other hand, 5-nucleotidase activity was increased strongly in areas where reticulum fibers had been deposited. Increase in nonspecific esterase and acid phosphatase in Kupffer cells indicated apparently a marked stimulation of the reticuloendothelial system.