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The Dedifferentiated Pattern of Enzymes in Livers of Tumor-bearing Rats¹

Department of Biological Chemistry, Harvard Medical School, and the Cancer Research Institute, New England Deaconess Hospital, Boston, Massachusetts 02215

Seven days after the s.c. implantation of a neoplasm, there are significant decreases of ornithine aminotransferase and glucokinase, as well as an increase of hexokinase in livers of adult rats. The concentration of 10 additional enzymes changes in the course of the following week, while the levels of nine other enzymes and the liver size remain normal. Growth of tumors in suckling rats inhibits the appearance of liver enzymes that normally emerge at this stage of differentiation. An implanted tumor inhibits the developmental formation in liver of ornithine aminotransferase, glucokinase, glutamine synthetase, and malate-NADP dehydrogenase, but it does not prevent glucocorticoids from inducing a premature rise of ornithine aminotransferase.

The enzymes that increase in host liver upon tumor transplantation are among those that are relatively high in fast-growing hepatomas and in fetal liver. Those that decrease are those that are low or absent in hepatomas and fetal liver. Thus, by gain or partial loss of these enzyme activities, the quantitative pattern of enzymes in host liver diverges from normal adult liver toward that of immature liver and the well-differentiated hepatomas.

¹ This study was supported by USPHS Grants CA-08676 and CA-05060 from the National Cancer Institute; by Grant HD-04532 from the National Institute of Child Health and Human Development; by Grant RR-05591 from the General Research Support Branch, Division of Research Resources; and by United States Atomic Energy Commission Contract AT(11-1)-3085 with the New England Deaconess Hospital.

Received 2/ 8/72. Accepted 5/18/72.

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