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Inhibition of Ascites Tumor Growth by 4-Aminopyrazolo-(3,4-d)pyrimidine in Combination with Azaserine, 6-Mercaptopurine, and Thioguanine^*

J. Frank Henderson and Irene G. Junga

( Department of Biological Sciences, Stanford Research Institute, Menlo Park, Calif.)

The effects of 4-aminopyrazolo(3,4-d)pyrimidine (APP), alone or in combination with azaserine, thioguanine, and 6-mercaptopurine, have been tested in Ehrlich ascites carcinoma, Sarcoma 180 ascites, 6C3HED ascites lymphosarcoma, Mecca ascites lymphosarcoma, and TA3 ascites carcinoma. The Ehrlich ascites carcinoma is the only tumor of this series which responds to APP. Several combinations of APP with azaserine, thioguanine, and 6-mercaptopurine resulted in additive or synergistic effects on Ehrilich carcinoma, Sarcoma 180, and 6C3HED lymphosarcoma. No combination was found which was effective against TA3 carcinoma.

Cross-resistance to APP was exhibited by two sublines of the Ehrlich carcinoma resistant to thioguanine and to 6-mercaptopurine.

1-Methyl-4-aminopyrazolo(3,4-d)pyrimidine (MeAPP) was active against Ehrlich ascites carcinoma and, when combined with azaserine, showed a synergistic response. MeAPP was not active against Sarcoma 180 ascites, nor was it synergistic in combination with azaserine for Sarcoma 180. A thioguanine-resistant subline of Ehrlich ascites carcinoma showed cross-resistance to MeAPP.

^* This work was supported by Contract No. SA-43-ph-3068 with the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, and by grants from the U.S. Public Health Service (CY-4551) and the Gustavus and Louise Pfeiffer Research Foundation.

Present address: Department of Pharmacology, The George Washington University School of Medicine, Washington, D.C.

Received 6/28/60.