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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.
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Medical oncology and tumor pharmacotherapy,
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Anticancer research,
T Ueda, and
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February 1981,
Gan,
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Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer,
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January 1980,
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer,
T Ueda, and
T Nakamura, and
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K Yamamoto, and
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October 1988,
Gan to kagaku ryoho. Cancer & chemotherapy,
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January 1989,
Chemotherapy,
T Ueda, and
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D Kagawa, and
K Yamamoto, and
M Uchida, and
M Sasada, and
H Uchino
June 1981,
Cancer research,
T Ueda, and
T Nakamura, and
D Kagawa, and
K Yamamoto, and
M Uchida, and
M Sasada, and
H Uchino
August 1977,
Cancer research,
