Summary
To explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA-deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 µmol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 µmol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 µmol/L deoxycytidine and from that of 10 µmol/L deoxyadenosine by 30 µmol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non-replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.
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Takeda, E., Kuroda, Y., Naito, E. et al. Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes. J Inherit Metab Dis 14, 87–95 (1991). https://doi.org/10.1007/BF01804395
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DOI: https://doi.org/10.1007/BF01804395