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

• Published in: Cancer research (Chicago, Ill.) Vol. 49; no. 2; pp. 309 - 313
• Main Authors: JAMIESON, G. P, SNOOK, M. B, BRADLEY, T. R, BERTONCELLO, I, WILEY, J. S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.01.1989
• 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; Antineoplastic agent; Adenocarcinoma; Human; Cell culture; Myelomonocytic leukemia; Ovary; Cell line; Antimetabolic; Biological transport; Intracellular; Tumor cell; Comparative study
• ISSN: 0008-5472; 1538-7445

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.