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Metabolic Effects of 9-Butyl-6-thioguanine in Vivo^*

( Life Sciences Research, Stanford Research Institute, Menlo Park, California)

The effects of 9-butyl-6-thioguanine (9-BTG)¹ on the utilization of preformed purines by the Ehrlich ascites tumor were studied in vivo. The results showed that 9-BTG inhibited the utilization of preformed purines for DNA synthesis under conditions in which RNA synthesis and the incorporation of glycine into proteins and nucleic acids were unaffected.

Studies on the incorporation of glycine-2-C¹⁴ and adenine-8-C¹⁴ into adenine nucleotides suggested that there was partitioning of the acid-soluble adenine into separate pools.

The synergistic effect obtained when 9-BTG and azaserine were combined for therapy of the Ehrlich ascites tumor can be explained on the basis that, of the two available sources of purine nucleotides for DNA synthesis, 9-BTG inhibits the utilization of host purines and azaserine blocks de novo purine synthesis.

^* This work was supported in part by Contract No. SA-43-ph-3068 with the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, and in part by United States Public Health Service Grant No. CY-4551.

A preliminary report of this work has been made (Proc. Am. Assoc. Cancer Res., 4:132, 1963).

¹ Abbreviations used: 9-BTG, 9-butyl-6-thioguanine; DNA, deoxyribonucleic acid; RNA, ribonucleic acid; AMP, ADP, ATP, adenosine mono-, di-, and triphosphates DPN, diphosphopyridine nucleotide.

Received 6/27/63.