[Verapamil inhibits the in vitro synthesis of DNA. I. Study of human lymphocyte cultures].

Verapamil in vitro reduced 3H-TdR incorporation into lymphocytes. High doses of Verapamil were lethal for cells; low doses inhibit DNA synthesis, but cell viability by the Trypan blue exclusion method is preserved. Increasing the concentration of Ca++ in the medium partially improved lymphocyte viability and 3H-TdR incorporation. Modification of the Na+ and K+ content in the medium did not interfere with Verapamil action. The inhibitory action was not completely reversible even when the cells were exposed to the drug for a short time (15'). Our results confirm the dependency of lymphocyte blast transformation on Ca++ during the first 20 h. Nifedipine did not inhibit cell replication, which suggests a different mechanism of action. Our investigation suggests that there is more than one model for calcium-antagonism and that the action of Verapamil can not be explained only by its influence on transmembrane Ca++ flux. We believe that Verapamil has a negative action on cell metabolism directly through an interaction on transmembrane Ca++ flux and on intracellular Ca++.