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Metabolic Effects of 9-D-Arabinosylpurines in Ascites Tumor Cells^*

( Life Sciences Research, Stanford Research Institute, Menlo Park, California)

Spongoadenosine (9-ß-D-arabinofuranosyladenine) was found to inhibit the growth of TA3 and 6C3HED ascites tumors. The growth of L1210 tumors was only slightly affected. Mice bearing implants of TA3 of 6C3HED cells, treated twice daily for 6 days with 25 mg/kg of arabinosyladenine, survived for more than 50 days, at which time they appeared to be tumor-free. Mice bearing L1210 cells survived only 11 per cent longer than did controls. Metabolic experiments using all three tumors demonstrated that the compound markedly reduced the incorporation of C¹⁴-labeled adenine, guanine, orotic acid, and glycine into the nucleic acids. The dominant effect was an inhibition of the utilization of precursors for DNA synthesis. Studies with arabinosyl-adenine-8-C¹⁴ in vivo indicated that the compound was readily phosphorylated to the triphosphate level from which arabinosylnucleotide was incorporated into the adenylic and guanylic acid components of RNA. No incorporation into DNA was observed with any of the tumors. Cleavage studies with the three tumors indicated that only L1210 cells were capable of cleaving the compound to a measurable extent. Treatment of TA3 and L1210 tumors with arabinosylguanine, at a lower but comparable level to arabinosyladenine, showed no significant difference in the relative effectiveness of the two compounds with respect to the incorporation of labeled precursors into the nucleic acids.

^* This work was supported in part by Contract No. SA-43-ph-3068 with the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, and in part by United States Public Health Service Grant No. CY-4551.

A preliminary report of part of this work has been made (Fed. Proc., 22:184, 1963).

Received 9/12/63.