METABOLISM AND DISTRIBUTION OF 9-BETA-D-ARABINOFURANOSYLADENINE IN MOUSE TISSUES.

9-β-d-Arabinofuranosyladenine (ara-A)[1][1] administered to normal mice at a dose level of 240 mg/kg/day for 6 days caused a 24 per cent loss in body weight. No change in the amount or distribution of leukocytes was found in blood during treatment. The drug was rapidly cleared from the blood and excreted in the urine as arabinosylhypoxanthine. It was demonstrated by use of ara-A-C14 that this compound was incorporated into the acid-soluble nucleotides and RNA of liver. No evidence for any cleavage of ara-A could be detected in the major organs or blood of normal mice, although deamination occurred rapidly. Treatment of subcutaneous solid tumors (TA3) with ara-A at 50 mg/kg/day caused only a slight inhibition of growth. No regression of the tumors occurred on halting treatment. A single dose of ara-A inhibited DNA biosynthesis for approximately 3 hours in L1210, 8 hours in TA3, and greater than 24 hours in 6C3HED ascites tumors. Treatment of TA3 ascites tumors with ara-G similarly depressed DNA synthesis. Only a 20 per cent increase in survival time was obtained with mice bearing TA3 ascites cells when treated with ara-G (50 mg/kg/day), compared with complete remission of this tumor with ara-A used at the same dose level. [1]: #fn-2