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Effects of purine antagonists on the metabolism of other purine antagonists

Authors
  • Henderson, J.Frank
  • Junga, Irene G.
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 1961
Volume
7
Issue
3
Pages
187–194
Identifiers
DOI: 10.1016/0006-2952(61)90085-5
Source
Elsevier
License
Unknown

Abstract

The effects of azaserine, thioguanine and 6-mercaptopurine on the metabolism of 4-aminopyrazolopyrimidine- 14C and of 4-aminopyrazolopyrimidine on the metabolism of thioguanine- 14C and of 6-mercaptopurine- 14C have been studied in Ehrlich ascites carcinoma and ascites sarcoma-180. Azaserine, thioguanine and 6-mercaptopurine not only enhanced the inhibition of tumor growth by 4-aminopyrazolopyrimidine, but also increased the amount of incorporation of the analog into tumor polynucleotides. Enhancement of the size of the pool of 4-aminopyrazolopyrimidine mononucloetides was evident during dual treatment with azaserine and thioguanine. The amount of incorporation of radioactivity from labeled 6-mercaptopurine into polynucleotides was decreased by 4-aminopyrazolopyrimidine, while little change in the size of the labeled mononucleotide pool was evident. The therapeutic effectiveness of thioguanine was increased by the co-administration of 4-aminopyrazolopyrimidine and the amount of incorporation of thioguanine into nucleic acids was somewhat increased by 4-aminopyrazolopyrimidine. These results are discussed with respect to present hypotheses concerning the anabolic conversion of purine analogs into their active derivatives.

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