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Effects of 4-Aminopyrazolo (3,4-d)pyrimidine and 1-Methyl-4-aminopyrazolo (3,4-d)pyrimidine on Nucleic Acid Purine Metabolism in Ascites Tumors^*

J. Frank Henderson and Irene G. Junga

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

The effect of a single injection of a therapeutic level of either 4-aminopyrazolo(3,4-d)pyrimidine or 1-methyl-4-aminopyrazolo(3,4-d)pyrimidine on the incorporation of glycine-C¹⁴, adenine-C¹⁴, or guanine-C¹⁴ into RNA and DNA adenine and guanine during the 12-hour period after drug administration has been studied in the Ehrlich ascites carcinoma, which is sensitive to both drugs, and in Sarcoma 180, which is resistant to both.

The results obtained show a rather complex series of events, varying markedly over the time course studied and often characterized by marked stimulations of isotope incorporation. Such effects lead to the tentative conclusions that the effects of these drugs are at the acid-soluble nucleotide level and that marked alterations occur in the pool sizes of these nucleotides.

^* 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.

A preliminary report of this work has been made (Proc. Am. Assoc. Cancer Research, 3:118, 1960).

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

Received 7/ 1/60.