1-β-d-Arabinofuranosylcytosine (araC) is an effective drug in the i.p. therapy of ovarian carcinoma but little is known of its transport and metabolism in this tumor. Influx of araC at 1 µm into cultured human ovarian carcinoma cells (CI 80-13S) was largely inhibited by nanomolar concentrations of the nucleoside transport inhibitor, nitrobenzylthioinosine, while the residual influx (approximately 10%) was inhibited only by micromolar concentrations of nitrobenzylthioinosine. There was a two fold greater density of specific [3H]nitrobenzylthioinosine binding to the nucleoside transporters on the ovarian than on cultured human leukemic cells (RC2a). Calculated turnover rates of the nucleoside transporter for 1 µm araC were 5-fold less in ovarian than in leukemic cells. The major metabolic product of araC was 1-β-d-arabinofuranosylcytosine 5′-triphosphate (araCTP) which accumulated in the ovarian cells to levels half those achieved in the leukemic cells. AraC was the major product of araCTP degradation in ovarian cells consistent with a pathway (araCTP →→ araCMP → araC) which is different from that previously found in leukemic cells (araCTP →→ araCMP → araUMP → araU). Despite these differences, ovarian carcinoma cells show substantial accumulation of araCTP from extracellular araC.

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This work was carried out during the tenure of a grant from the Anti-Cancer Council of Victoria. We also thank The Upjohn Company for their support.

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