Consequences of adenosine deaminase deficiency on thymocyte metabolism

Abstract

Using 2′-deoxycoformycin inhibition of adenosine deaminase as a model of adenosine deaminase deficiency, the effects of 10 μM 2′-deoxyadenosine (dAdo) on the metabolism of concanavalin A (Con A)-stimulated rat thymocytes were studied. When dAdo and Con A were added simultaneously, a strong inhibition of the incorporation of [³H]thymidine (84%); [³H]uridine (98%) and L-[³H] leucine (46%) in the acid-insoluble fraction, and of [¹⁴C]formate (78%) and H¹⁴CO₃⁻ (43%) uptake is observed after 48 h of incubation. When dAdo is added after 12 h of Con A stimulation, no such inhibition is observed, but when added after 24 h of stimulation, there is an enhancement of blastogenesis as measured by nucleic acid, protein, and purine and pyrimidine base synthesis. More detailed studies of thymocytes stimulated by Con A for 0–72 h, followed by short-term incubation periods with dAdo (1–5 h), revealed that thymocyte metabolism becomes progressively less sensitive to dAdo-mediated inhibition during the course of blastogenesis.