Effect of long-term zidovudine exposure on salvage and de novo purine and pyrimidine nucleotide syntheses

Salvage and de novo purine and pyrimidine nucleotide syntheses were studied in H⁹ (a human lymphoid cell line) and H_9-AZT cells (chronically zidovudine-exposed H₉ cells). H_9-AZT cells incorporated 18% and 27% more hypoxanthine and uridine, respectively, than H₉ cells. The incorporation of the formate and bicarbonate was similar in both cell lines. Purine and pyrimidine de novo synthesis was inhibited by hypoxanthine and uridine, respectively. Hypoxanthine and uridine salvage pathways, however, were not affected by formate or bicarbonate. Short-term AZT exposure of cells had no effect on nucleotide synthesis. Some of the problems encountered in the studies of purine and pyrimidine synthesis are also discussed.