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Effects of Combinations of Azaserine and of 6-Diazo-5-oxo-L-norleucine with Purine Analogs and Other Antimetabolites on the Growth of Two Mouse Mammary Carcinomas

( Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, and the Sloan-Kettering Division of Cornell University Medical College, New York, N.Y.)

1. Combined treatment of mice bearing the RC mammary carcinoma with azaserine or DON, on the one hand, and 6-mercaptopurine, 6-methyl-mercaptopurine, 6-chloropurine, and thioguanine, on the other, caused a significantly greater number of complete tumor regressions and produced a synergistically increased inhibitory effect on tumor growth.

2. More tumor regressions after combined therapy were observed when treatment started on the next day following implantation of the RC carcinoma than in the cases when treatment was initiated 4 days later.

3. No synergistic therapeutic response could be elicited with these combinations of chemicals in the mouse mammary carcinoma S-790.

4. Therapy of the RC carcinoma with combinations of azaserine or DON and A-methopterin, deoxypyridoxine, N-methylformamide, ß-2-thienylalanine, or purine hydrochloride produced no synergistic therapeutic response.

5. Subcutaneous administration of cortisone to the mice bearing RC carcinoma subsequent to their treatment with 6-mercaptopurine, thioguanine, or 6-mercaptopurine and azaserine markedly decreased the number of complete tumor regressions, which observation indicated that some presumably immunogenetic factors may contribute to the causation of tumor regression in chemically treated mice.

6. Several purines, amino acids, and vitamins were tested for their ability to counteract the inhibition of growth of the RC carcinoma caused by DON. Only adenine was found to be partially effective in this respect.

Received 7/ 8/57.