Transport and metabolism of 1-beta-D-arabinofuranosylcytosine in human ovarian adenocarcinoma cells

Cancer Res. 1989 Jan 15;49(2):309-13.

Abstract

1-beta-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 microM 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 microM araC were 5-fold less in ovarian than in leukemic cells. The major metabolic product of araC was 1-beta-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Aged
  • Arabinofuranosylcytosine Triphosphate / metabolism
  • Binding Sites
  • Cell Line
  • Cytarabine / metabolism*
  • Female
  • Humans
  • Leukemia, Myelomonocytic, Acute / metabolism
  • Male
  • Ovarian Neoplasms / metabolism*
  • Thioinosine / analogs & derivatives
  • Thioinosine / metabolism

Substances

  • Cytarabine
  • Arabinofuranosylcytosine Triphosphate
  • Thioinosine
  • 4-nitrobenzylthioinosine