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Basic Sciences

Transport and Metabolism of 1-β-d-Arabinofuranosylcytosine in Human Ovarian Adenocarcinoma Cells

G. P. Jamieson, M. B. Snook, T. R. Bradley, I. Bertoncello and J. S. Wiley
G. P. Jamieson
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M. B. Snook
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T. R. Bradley
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I. Bertoncello
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J. S. Wiley
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DOI:  Published January 1989
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Abstract

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.

Footnotes

  • ↵1 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.

  • ↵2 To whom requests for reprints should be addressed.

  • Received February 23, 1988.
  • Revision received August 4, 1988.
  • Accepted September 26, 1988.
  • ©1989 American Association for Cancer Research.
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January 1989
Volume 49, Issue 2
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Transport and Metabolism of 1-β-d-Arabinofuranosylcytosine in Human Ovarian Adenocarcinoma Cells
G. P. Jamieson, M. B. Snook, T. R. Bradley, I. Bertoncello and J. S. Wiley
Cancer Res January 15 1989 (49) (2) 309-313;

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Transport and Metabolism of 1-β-d-Arabinofuranosylcytosine in Human Ovarian Adenocarcinoma Cells
G. P. Jamieson, M. B. Snook, T. R. Bradley, I. Bertoncello and J. S. Wiley
Cancer Res January 15 1989 (49) (2) 309-313;
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