Abstract
The toxicity of 3′-azidothymidine (AZT) in human lymphocytes has been shown previously to be reversed by co-incubation with the ribonucleosides cytidine or uridine. In the present paper, the effects of 3′-azidothymidine and cytidine/uridine, both alone and in combination, were studied upon key processes in lymphocytes in order to discover more about the mechanism of toxicity reversal.
In these experiments 3′-azidothymidine had only minor effects on the ribonucleoside triphosphate pools. Cytidine increased the CTP pool, and uridine the UTP pool. Co-incubation with AZT caused similar changes to incubation with cytidine or uridine alone. Toxicity reversal was not linked to replacement of deficient ribonucleoside triphosphate pools.
3′-Azidothymidine caused the excretion of thymidine from lymphocytes. Incubation with cytidine and uridine increased the intracellular cytidine and uridine pools, respectively. Co-incubation with 3′-azidothymidine increased still further the intracellular cytidine and uridine pools. Cytidine and uridine did not affect the intracellular 3′-azidothymidine pool.
The toxicity of 3′-azidothymidine was increased by co-incubation with the bases adenine, guanine, hypoxanthine, and uracil, but not by dihydrouracil, thymine, or xanthine.