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The Inhibition of L5178Y Lymphoma Cells by Combinations of Cortisone and Actinomycin D¹

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut

The treatment of mice bearing L5178Y lymphoma ascites cells with combinations of actinomycin D and cortisone resulted in a pronounced decrease in the number of viable neoplastic cells; this, in turn, resulted in a marked depression of the number of lymphomatous cells in the peritoneal cavity. The degree of inhibition achieved by the mixture of the 2 agents was greater than that produced by either drug alone. Biochemical changes associated with the cell death produced by these agents in combination was studied by measuring the effects of actinomycin D and cortisone alone and in combination on the average cellular content of deoxyribonucleic acid, ribonucleic acid, and residual protein. A depletion of the cellular content of nucleic acids and proteins was induced by combinations of these agents; RNA was the most sensitive, and both the degree and duration of the depression of the cellular content of RNA induced by simultaneous exposure of cells to actinomycin D and cortisone was greater than that of DNA or protein. It is suggested that the carcinolysis produced by combinations of cortisone and actinomycin D reflects, in part, a complementary inhibitory process involving RNA and that the resultant metabolic imbalance leads to cell death.

¹ This research was supported by Grant CA-02817 from the National Cancer Institute, USPHS.

² Postdoctoral support provided by the Anna Fuller Fund; present address, Department of Surgery I, University of Kanazawa, Kanazawa, Japan.

Received 6/10/65.