The DNA, RNA, and protein contents, and the incorporation of cytidine-3H and 1-β-d-arabinofuranosylcytosine-3H in suspensions of human leukemic leukocytes and normal bone marrow cells were studied. After treatment with 1-β-d-arabinofuranosylcytosine, 4 of 6 patients with leukemia showed significant response in terms of a reduction of greater than 90 percent in peripheral leukemic cell count. The leukocytes of these subjects exhibited reduced DNA and elevated RNA and protein contents; uptake of cytidine-3H into DNA was depressed, whereas, the specific activity of RNA was increased. On the other hand, in preparations of normal bone marrow cells from 5 of 6 treated patients, DNA, RNA, and protein contents all increased, while inhibition of DNA synthesis was observed in only 2 subjects. Treatment with the analog also increased the uptake of cytidine-3H into the RNA of bone marrow cells. Studies carried out with leukocytes exposed to 1-β-d-arabinofuranosylcytosine in vitro showed that the uptake of cytidine-3H into RNA was increased and that into DNA was depressed. Examination of nucleic acids and their hydrolysates, obtained from leukemic cells exposed to 1-β-d-arabinofuranosylcytosine-3H, indicated that only limited incorporation of the compound occurred, despite extensive intracellular conversion to nucleotides. Deoxycytidine, an antagonist of 1-β-d-arabinofuranosylcytosine, profoundly inhibited the uptake of the nucleoside by leukemic leukocytes, and had a lesser, though still marked effect, on its incorporation into nucleic acids.

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This investigation was supported in part by Grants CA-8341 and CA-5138 of the USPHS and T-335C of the American Cancer Society.

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