Differences in deoxyadenosine metabolism in human and mouse lymphocytes.

Abstract Deoxyadenosine has been implicated in the pathogenesis of the immune dysfunction associated with a genetic deficiency of adenosine deaminase. In the course of experiments aimed at finding an animal model in which to study in vivo deoxyadenosine toxicity, we have noted that human and mouse lymphocytes metabolize deoxyadenosine differently. In extracts of mouse tissues, deoxyadenosine phosphorylating activity was widespread, analogous to the tissue distribution of adenosine kinase. On the contrary, in extracts of human tissues, deoxyadenosine phosphorylating activity was found primarily in the thymus, similar to the tissue distribution of deox-ycytidine kinase. In intact mouse lymphocytes, deoxyadenosine phosphorylation at low concentrations was inhibited by adenosine, but not by deoxycytidine. In intact human lymphocytes, deoxyadenosine phosphorylation at low concentrations was inhibited more by deoxycytidine than by adenosine. Hence, at low but pharmacologically important substrate concentrations, the lymphospecific enzyme deoxycytidine kinase was more important in phosphorylating deoxyadenosine in human than in mouse lymphocytes. These results suggest that the tissue distribution and toxicity of exogenously administered deoxyadenosine and related analogues could differ in mouse and man.