Transport of uridine and 3-deazauridine in cultured human lymphoblastoid cells

The transport of uridine and 3-deazauridine was compared in two lines of cultured human lymphoblastoid cells that differ in their sensitivity to 3-deazauridine apparently because of reduced uridine-cytidine kinase activity in the resistant line. The kinetic parameters (+/- S.E.) of uridine transport...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1984, Vol.44 (1), p.161-165
Main Authors: DAHLIG-HARLEY, E, PATERSON, A. R. P, ROBINS, M. J, CASS, C. E
Format: Article
Language:English
Subjects:
3-deazauridine
3-Deazauridine - metabolism
Antineoplastic agents
Biological and medical sciences
Biological Transport
Cell Line
General aspects
Humans
Hydrogen-Ion Concentration
Kinetics
Leukemia, Lymphoid
lymphoblastoid cell lines
man
Medical sciences
Pharmacology. Drug treatments
uridine
Uridine - analogs & derivatives
Uridine - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The transport of uridine and 3-deazauridine was compared in two lines of cultured human lymphoblastoid cells that differ in their sensitivity to 3-deazauridine apparently because of reduced uridine-cytidine kinase activity in the resistant line. The kinetic parameters (+/- S.E.) of uridine transport were similar in the two cell lines: Km, 0.23 +/- 0.02 and 0.25 +/- 0.07 mM; and Vmax, 35 +/- 2 and 57 +/- 10 pmol/microliter of cell water per sec, respectively, for 6410/MP (parental) and 6410/MP/DU (resistant) cells. 3-Deazauridine, while transported with similar kinetic characteristics in both cell lines, was not as good a substrate for the nucleoside transporter as was uridine, and its transport was dependent on pH. Kinetic parameters, determined using calculated concentrations of the undissociated form of 3-deazauridine (pKa, 6.5), were: Km, 0.52 +/- 0.01 and 0.51 +/- 0.03 mM; and Vmax, 28 +/- 0.5 and 24 +/- 0.9 pmol/microliter of cell water per sec, respectively, for 6410/MP and 6410/MP/DU cells. At pH 8, a condition in which 97% of 3-deazauridine molecules are ionized, rates of transport were almost zero. It is concluded that the undissociated form of 3-deazauridine is the substrate for the nucleoside transporter.
ISSN:0008-5472
1538-7445