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Molecular Pharmacology

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Research ArticleArticle

Thymidine Induced Perturbations in Ribonucleoside and Deoxyribonucleoside Triphosphate Pools in Human Leukemic CCRF-CEM Cells

GERALD B. GRINDEY, MING C. WANG and JAMES J. KINAHAN
Molecular Pharmacology September 1979, 16 (2) 601-606;
GERALD B. GRINDEY
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263
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MING C. WANG
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263
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JAMES J. KINAHAN
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263
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Abstract

The inhibition of growth of CCRF-CEM cells in culture by various concentrations of thymidine was correlated with alterations in the intracellular concentration of deoxyribonucleoside triphosphates. With increasing growth inhibition, the concentrations of dTTP, dGTP and dATP all increased while that of dCTP decreased somewhat. Although there was a linear relationship between the decrease in growth rate and the concentration of dCTP, the change in the pool of dCTP does not appear to be of sufficient magnitude to account for the growth inhibition. The addition of deoxycytidine (3 to 10 µM) completely reversed the growth inhibition produced by thymidine. Higher concentrations of deoxycytidine (20 µM), however, again produced a 13% inhibition of growth rate in the presence of thymidine. The intracellular concentrations of dCTP and dATP were equal to control values; those of dTTP and dGTP were increased. The results indicate that small perturbations in the deoxynucleosides triphosphate pools inhibit cellular growth and that increases as well as decreases in these pools may inhibit DNA synthesis as mediated through their interaction with DNA polymerase.

  • Copyright © 1979 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 16, Issue 2
1 Sep 1979
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Research ArticleArticle

Thymidine Induced Perturbations in Ribonucleoside and Deoxyribonucleoside Triphosphate Pools in Human Leukemic CCRF-CEM Cells

GERALD B. GRINDEY, MING C. WANG and JAMES J. KINAHAN
Molecular Pharmacology September 1, 1979, 16 (2) 601-606;

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Research ArticleArticle

Thymidine Induced Perturbations in Ribonucleoside and Deoxyribonucleoside Triphosphate Pools in Human Leukemic CCRF-CEM Cells

GERALD B. GRINDEY, MING C. WANG and JAMES J. KINAHAN
Molecular Pharmacology September 1, 1979, 16 (2) 601-606;
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