A novel effect of the new antileukemic drug, 2-chloro-2'-deoxyadenosine, in human lymphocytes

2-chloro-2'-deoxyadenosine (Cl-dAdo) is a potent drug against hairy cell leukemia and other lymphomas. Its effects on the metabolism of labeled deoxycytidine (5-[3H]dCyd) and deoxythymidine ([3H]dThd) were investigated in short term cultures of human lymphocytes. In the presence of Cl-dAdo, a more pronounced inhibition of DNA synthesis was found, accompanied with a much higher accumulation of radioactivity in dTTP than in dCTP. This difference disappeared in the presence of exogenous dThd. Analysis of intracellular metabolites of 5-[3H]dCyd showed an increase in [3H]dCTP used for liponucleotide biosynthesis and a decrease in [3H]dUMP formation in the presence of Cl-dAdo, suggesting the possible inhibition of dCMP deaminase.