Biochemical and Immunological Evaluation of Long Term Coformycin Administration in the Mouse

Abstract

The inherited human deficiency of adenosine deaminase is associated with severe combined immunodeficiency disease^1,2. Coformycin is a potent inhibitor of adenosine deaminase and markedly potentiates the in vitro toxicity of adenosine and deoxyadenosine toward lymphoid cells. We wished to evaluate some of the biochemical and immunological events associated with coformycin administration in vivo. Increased dATP concentrations observed in adenosine deaminase deficiency³ are thought to inhibit ribonucleotide reductase and thereby restrict DNA synthesis. Another secondary consequence of a deficiency of adenosine deaminase may be inhibition of S-adenosylhomocysteine hydrolase by de oxyadenosine⁴.