Metabolic Effects of 9-butyl-6-thioguanine in Vivo.

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 UNA 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 utiliza tion of host purines and azaserine blocks de novo purine synthesis.