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Histochemical and Microchemical Changes in Experimental Cirrhosis and Hepatoma Formation in Mice by Carbon Tetrachloride^{* ,}

R. E. Stowell, C. S. Lee, K. K. Tsuboi and A. Villasana

( Departments of Pathology and Oncology, University of Kansas Medical School, Kansas City, Kansas, and Department of Pathology, Washington University School of Medicine, St. Louis, Mo.)

Some of the changes in mouse livers after repeated bi-weekly feedings of carbon tetrachloride were studied by histochemical and microchemical methods during the development of cirrhosis and in hepatomas. Samples of liver tissue from various mice, and hepatomas from the same and different mice, showed considerable variation.

The liver cells that survive a single injection of carbon tetrachloride show evidence of a disturbed metabolism of glycogen and lipids. Glycogen is increased in the later stages of cirrhosis and in most hepatomas. The lipid content of both cirrhotic and hepatoma tissues is much less than that of normal liver from animals on fast. Some of the hepatomas had more lipids than the adjacent cirrhotic tissue. Fat was observed in the nuclei of some liver cells. The cholesterol content of the liver decreased during the third- to twelfth-week stages of cirrhosis development. Alkaline phosphatase is usually increased in cirrhotic tissue and to an even greater extent in hepatomas. The water content of the hepatomas was higher than in the cirrhotic liver.

In cirrhotic and hepatoma tissue the content of both the nucleic acids varies in individual cases. The observed increase in desoxypentosenucleic acid in some cirrhotic livers and hepatomas may be explained by the increased content of nuclei of fibroblasts and inflammatory cells. Chemical measurements of pentosenucleic acid were higher in hepatomas than in adjacent cirrhotic tissue.

Histochemical observations showed esterase to be slightly increased in cirrhosis and frequently decreased in hepatomas, whereas the chemical findings were variable in all tissues. The chemical studies of nitrogen, phosphorus, acid phosphatase, and succinoxidase did not show significant changes.

A yellow pigment similar to ceroid was observed in both the short- and long-term studies. Occasional heterotopic bone formation in cirrhotic areas was noted.

^* Aided by grants from the National Cancer Institute, Atomic Energy Commission, and American Cancer Society on recommendation of the Committee on Growth of the National Research Council.

Presented at the meeting of the American Association for Cancer Research in Detroit, April 16, 1949.

Post-doctoral fellow, National Institutes of Health, 1949–50. Present address, Department of Pathology, Union Hospital, Hankow, Hupeh, China.

Present address, Calle Nueve No. 73, San Pedro de los Pinos, Mexico, D.F., Mexico.

Received 12/22/50.