Intracellular distribution of N4-behenoyl-1-beta-D-arabinofuranosylcytosine in blood cells.
In order to clarify differences in mode of action between N4-behenoyl-1-beta-D-arabinofuranosylcytosine (behenoyl-ara-C) and 1-beta-D-arabinofuranosylcytosine (ara-C), comparative studies on both agents were undertaken. When human erythrocytes incubated with behenoyl-ara-C[acyl-1-14C] were fractionated into stroma and stroma-free lysate, a marked accumulation of radioactivity in stroma was observed. In contrast, ara-C[cytosine-2-14C] was rapidly incorporated into the stroma-free lysate. Thin-layer chromatography of the extracts of L1210 cells incubated with behenoyl-ara-C[acyl-1-14C] or behenoyl-ara-C[cytosine-2-14C] at 37 degrees for 60 min revealed that most of the incorporated drug remained as unmetabolized behenoyl-ara-C. After incubation of 20 microM behenoyl-ara-C or ara-C with L1210 cells at 37 degrees for 60 min, subcellular fractionation of the cell suspension was performed; behenoyl-ara-C was accumulated markedly in the membrane, mitochondria and microsome fractions. In contrast, most of the ara-C was found in the 105,000g supernatant fraction. The accumulation of behenoyl-ara-C in membrane structures may result from the lipophilic nature of the agent, which may have a prolonged inhibitory action on leukemic cell proliferation.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains
D000970:Antineoplastic Agents; D003561:Cytarabine; C015019:enocitabine