Consequences of adenosine deaminase deficiency on thymocyte metabolism

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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.