Biochemical and pharmacological studies with 1-β- d-arabinofuranosylcytosine in man

Cytosine arabinoside, labeled with tritium, was administered to five patients with far-advanced neoplasms. The analog was rapidly deaminated to uracil arabinoside; the latter accounted for between 86 and 96 per cent of the radioactivity excreted in the urine. Incorporation of tritium-labeled cytidine into DNA by suspensions of human leukemic leukocytes was inhibited in the presence of cytosine arabinoside. Although administration of cytosine arabinoside at therapeutic levels depressed the ability of leukemic leukocytes to incorporate cytidine into DNA in vitro, there was no correlation between the degree and duration of this effect and the clinical response to the drug. Tritium-labeled cytosine arabinoside entered human leukemic leukocytes very rapidly when incubated with the cells in vitro; there was a small but significant incorporation of the analog into both DNA and RNA.