9-β-D-ARABINOFURANOSYLADENINE AS AN INHIBITOR OF METABOLISM IN NORMAL AND NEOPLASTIC CELLS

Abstract

Treatment of L1210 ascites tumors in vivo with combinations of 9-β-D-arabinosyladenine and 6-methyladenine nucleosides repressed cell growth by approximately 30%. This repression was measured by the volume of accumulated cells after 6 days of treatment with these compounds. No significant increase of the survival time of L1210 tumor-bearing mice was obtained when the mice were treated under identical conditions. Incubation of TA3 or L1210 ascites cells in vitro with 6-methyIadenosine inhibited the deamination of added arabinosyladenine by 95% for TA3 and 50% for L1210. The cleavage of adenosine or deoxyadenosine in the presence of arabinosyladenine was unaffected. Incorporation of C14-adenine or C14-uracil into the DNA of TA3 cells was inhibited when arabinosyladenine and the four natural deoxynucleosides were incubated in vitro. This inhibition was relieved specifically by adenosine but not by deoxyadenosine. Arabinosyladenine affected the uptake of C14-amino acids into the proteins of TA3 cells and liver. Elevation or depression of incorporation varied with the amino acid used. Incorporation of arabinosyladenine-C14into the RNA of subcellular components of TA3 and liver cells was greatest in the nuclear and soluble fractions.