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

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 concentratio...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1989-01, Vol.49 (2), p.309-313
Main Authors: JAMIESON, G. P, SNOOK, M. B, BRADLEY, T. R, BERTONCELLO, I, WILEY, J. S
Format: Article
Language:English
Subjects:
Adenocarcinoma - metabolism
Aged
Antineoplastic agents
Arabinofuranosylcytosine Triphosphate - metabolism
Binding Sites
Biological and medical sciences
Cell Line
Cytarabine - metabolism
Female
General aspects
Humans
Leukemia, Myelomonocytic, Acute - metabolism
Male
Medical sciences
Ovarian Neoplasms - metabolism
Pharmacology. Drug treatments
Thioinosine - analogs & derivatives
Thioinosine - metabolism
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Summary: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.
ISSN:0008-5472
1538-7445