Stimulatory Effects of Inosine and Deoxyinosine on the Incorporation of Uracil-2-14C, 5-Fluorouracil-2-14C, and 5-Bromouracil-2-14C into Nucleic Acids by Ehrlich Ascites Tumor Cells in Vitro

Antonio Gotto, M. L. Belkhode, O. Touster

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The incorporation of uracil-2-14C into the nucleic acids of Ehrlich ascites tumor cells is increased 10- to 50-fold by the addition of inosine. Maximum stimulation is obtained at an inosine concentration of 1 mm. Actinomycin D (50 μg/ml) abolishes incorporation. The effect of inosine seems unlikely to be mediated by an enhancement of synthesis of ATP, 5-phosphoribosyl-1-pyrophosphate, or nucleic acids by de novo pathways. Unlike uracil incorporation, the labeling of nucleic acid by uridine-2-14C is extensive in the absence of inosine. The incorporation of 5-fluorouracil-2-14C into RNA also is greatly increased by inosine. Inosine has little effect on the incorporation of 5-bromouracil-2-14C into nucleic acids, whereas deoxyinosine is a potent stimulator. Deoxyinosine, on the other hand, is a relatively weak enhancer of uracil incorporation. These results suggest that ribose-1-phosphate and deoxyribose-l-phosphate may be rate limiting for the incorporation of uracil (or 5-fluorouracil) and 5-bromouracil into RNA and DNA respectively. Inosine and deoxyinosine serve as precursors of ribose-1-phosphate and deoxyribose-1-phosphate These interconversions involve purine and pyrimidine nucleoside phosphorylases. The possible application of these findings in chemotherapy is discussed.

Original languageEnglish (US)
Pages (from-to)807-811
Number of pages5
JournalCancer research
Volume29
Issue number4
StatePublished - Jan 1 1969

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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