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Alterations in Enzymes of Amino Acid Catabolism in Livers of Rats Bearing the Morris 7800 Hepatoma¹

Departments of Oncology [G. de R., H. C. P.] and Pathology [H. C. P.], McArdle Laboratory for Cancer Research, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

The activities of the amino acid-catabolizing enzymes, serine dehydratase (EC 4.2.1.16), ornithine aminotransferase (EC 2.6.1.13), tyrosine aminotransferase (EC 2.6.1.5), and alanine aminotransferase (EC 2.6.1.12), were measured in the livers of rats bearing the Morris 7800 hepatoma for varying periods. A relatively rapid decrease in the activities of hepatic serine dehydratase and ornithine aminotransferase beginning within 1 week after inoculation of the tumor into the host was observed. The levels of tyrosine and alanine aminotransferases remained comparable to that in livers of non-tumor-bearing animals for approximately 4 weeks after the inital tumor transplantation.

The induction of serine dehydratase and tyrosine aminotransferase by glucagon was studied in these tumorbearing animals. The response of serine dehydratase to this hormone decreased progressively with time after inoculation of the neoplasm. By 30 days after tumor inoculation, no response of this enzyme to glucagon administration was elicited. Tyrosine aminotransferase in these rats, on the other hand, was still inducible at least 5-fold at 35 days after tumor transplantation. By 14 days of tumor growth, ornithine aminotransferase activity was decreased in kidney and muscle as well as liver, although no changes in alanine aminotransferase activity in these tissues of the host could be detected. These results lend further support to the concept that highly differentiated hepatocellular carcinomas induce selective effects in host tissues, reflected by alterations in the levels of these four enzymes of amino acid catabolism.

¹ This work was supported in part by Grant CA-07175 from the National Cancer Institute.

² Damon Runyon-Walter Winchell Fellow in Cancer Research, 1974 to 1976. Present address: Department of Nutrition, College of Agricultureal and Environmental Sciences, University of California at Davis, Calif. 95616.

Received 9/ 6/77. Accepted 1/11/78.