Studies on the Effects of Hydroxyurea and Other Anticancer Drugs upon Pyrimidine Metabolism

William Ralph Vogler, Susan Horwitz, D. P. Groth

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The reversal of azauridine-induced oroticaciduria by hydroxyurea has been studied to further elucidate the control mechanisms involved in the de novo pathways of pyrimidine biosynthesis. No direct effect of hydroxyurea upon partially purified aspartate transcarbamylase and dihydroorotase was observed. Hydroxyurea selectively inhibited the incorporation of 14C-labeled aspartate, orotate, and formate into the DNA bases of human leukemic cells incubated in vitro. No effect of hydroxyurea was observed in the RNA bases isolated from these leukemic cells. Other chemotherapeutic agents, including 5-iododeoxyuridine, 5-fluorodeoxyuridine, Methotrexate, cytosine arabinoside, and cyclophosphamide, were administered to patients receiving 6-azauridine. Only Methotrexate and cyclophosphamide inhibited orotic acid excretion in a manner similar to hydroxyurea. These results suggest that the control of pyrimidine biosynthesis is linked to DNA synthesis or function in an as yet unexplained manner.

Original languageEnglish (US)
Pages (from-to)1371-1378
Number of pages8
JournalCancer Research
Volume29
Issue number7
StatePublished - Jul 1 1969
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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