Publications & Reports

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

G P Jamieson, M B Snook, T R Bradley, I Bertoncello, J S Wiley
Department of Haematology, Austin Hospital, Heidelberg, Melbourne, Australia.

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

  • Journal: Cancer Research
  • Published: 15/01/1989
  • Volume: 49
  • Issue: 2
  • Pagination: 309-313

Author