Molecular Pharmacology, Vol 1, 231-238, Copyright © 1965 by the American Society for Pharmacology and Experimental Therapeutics

Some Inhibitory Effects of 9--D-Xylofuranosyladenine, an Adenosine Analog, on Nucleotide Metabolism in Ascites Tumor Cells

¹ Life Sciences Research, Stanford Research Institute, Menlo Park, California

Xylosyl adenine (XA) was found to prolong the survival time of mice bearing TA3 or Ehrlich ascites cell tumors. Experiments with either TA3 or Ehrlich cells demonstrated that XA markedly inhibited the incorporation of ¹⁴C-labeled adenine or glycine into both RNA and DNA.

XA was relatively rapidly converted in vivo and in vitro to the triphosphate (XATP).

XA was as effective as adenosine as a feedback inhibitor of purine synthesis.

XATP was found to be profoundly inhibitory to the formation of 5-phosphoribosyl-1-pyrophosphate (PRPP). This effect on the PRPP supply appeared to be the most likely explanation for the inhibitory effects on RNA and DNA synthesis, and for the inhibition of cell growth.

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ACKNOWLEDGMENT This work was supported by Contract No. PH-43-65-575 with the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health.