Inhibition of ascites tumor growth by 4-aminopyrazolo-(3,4-d)pyrimidine in combination with azaserine, 6-mercaptopurine, and thioguanine.

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 TAS 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 Ehrlich 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-arninopyrazolo(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 combi nation with azaserine for Sarcoma 180. A thioguanine-resistant subline of Ehrlich ascites carcinoma showed cross-resistance to MeAPP.