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.