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Responsiveness of Two Urea Cycle Enzymes in Morris Hepatomas to Metabolic Modulations¹

Department of Biological Chemistry and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48104, and Department of Biochemistry, College of Medicine, Howard University, Washington, D. C. 20001

Arginase and argininosuccinate synthetase activities have been assayed in some 14 hepatomas and the corresponding host livers. The hepatomas exhibited an extremely wide range of activities of the two enzymes of the urea cycle. A good correlation exists between the activities of the two enzymes in the hepatomas. However, the activity of either enzyme in the hepatomas bears no correlation with that in the host livers. Moreover, there is no correlation between the enzyme activity and the growth rate or chromosome number of the hepatomas.

Cortisol raised arginase activity to a larger degree in Hepatomas 7800 and 8999 than in the host livers, but the hormone enhanced argininosuccinate synthetase activity more in the host livers than in the two hepatomas. Thyroxine increased arginase activity in Hepatoma 7800 and the host liver of intact rats but decreased it in adrenalectomized rats. The thyroid hormone also elevated the synthetase activity in Hepatoma 7800 but not in the host liver. On the other hand, thyroxine did not affect the activity of these two enzymes in either Hepatoma 9618A or the host liver.

While actinomycin D or cycloheximide blocked the hormone-induced increase in arginase activity of Hepatomas 7800 and 8999 and in the synthetase activity of Hepatoma 7800, the antibiotics exerted no inhibitory effect on the enzymes in the host livers. Increasing the protein content of the diet elicited increases in the activity of the two enzymes in Hepatoma 9618A, as well as in the host liver, but not in Hepatoma 8999.

These results together with others show an overresponse by enzymes in hepatomas, when compared with the response by the same enzymes in host livers. This overresponsiveness is discussed as a manifestation of deranged control mechanisms in cancer.

¹ This work was supported in part by Grant AM-07319 from the National Institute of Arthritis and Metabolic Diseases and Grant CA-10729 from the National Cancer Institute, USPHS.

Received 5/27/70. Accepted 9/18/70.