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Some Urea Cycle Enzymes and Amino Acyl-RNA Synthetases of Rat Hepatomas¹

Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan 48104

Three urea cycle enzymes, argininosuccinate synthetase, argininosuccinate lyase, and arginase, and two amino acyl-RNA synthetases, the glutamyl and the glutaminyl enzymes, have been studied in the Novikoff hepatoma and Morris Hepatomas 7787, 7793, and 7800. Except for Hepatoma 7793, which had "normal" activities of the 3 urea cycle enzymes, other hepatomas had lower activities than normal liver. The slow-growing Hepatoma 7787 possessed even lower argininosuccinate synthetase activity than the fast-growing Novikoff hepatoma, making urea synthesis an almost completely deleted mechanism in Hepatoma 7787.

Argininosuccinate synthetase activity declined in the regenerating liver. It rose in the hepatomas of adrenalectomized and diabetic rats. Cortisol raised the enzyme activity in Hepatomas 7800 and 7787, but lowered it in Hepatoma 7793.

All the hepatomas examined also had lower activities of the 2 amino acyl-RNA synthetases than normal liver. Arranged in the order of decreasing activities, Hepatoma 7800 led Hepatoma 7793, Hepatoma 7787, and Novikoff hepatoma. Although lower enzyme activities were found in the hepatomas, higher activities were observed in the regenerating liver. Evidently, malignant growth and controlled growth can elicit biochemical changes irrelevant to each other.

Cortisol injection elevated the amino acyl-RNA synthetases, particularly the glutaminyl enzyme, in Hepatoma 7800 above the activities found in normal liver. However, the hormone did not raise the enzyme activities in either Hepatoma 7793 or Hepatoma 7787. The increase in enzyme activity due to cortisol in Hepatoma 7800 appears to reflect de novo synthesis of the enzyme.

The results of this study have shown that the growth rate of a hepatoma cannot serve as an index for projecting the degree of deviations in biochemical characteristics of that hepatoma from those of normal liver, and that the slow-growing Morris hepatomas, as a group, possess divergent biochemical properties often eliciting contrasting responses to metabolic manipulations.

¹ This work was supported in part by Research Grants CA-01719 and AM-07319 from the NIH, USPHS; and by funds from a special appropriation for cancer research from the State Legislature.

Received 11/14/66. Accepted 1/ 1/67.