EFFECT OF LONG-TERM ZIDOVUDINE EXPOSURE ON SALVAGE AND DE-NOVO PURINEAND PYRIMIDINE NUCLEOTIDE SYNTHESES

Salvage and de novo purine and pyrimidine nucleotide syntheses were st udied in H-9 (a human lymphoid cell line) and H-9-AZT cells (chronical ly zidovudine-exposed H-9 cells). H-9-AZT cells incorporated 18% and 2 7% more hypoxanthine and uridine, respectively, than H-9 cells. The in corporation of the formate and bicarbonate was similar in both cell Li nes. Purine and pyrimidine de novo synthesis was inhibited by hypoxant hine and uridine, respectively. Hypoxanthine and uridine salvage pathw ays, however, were not affected by formate or bicarbonate. Short-term AZT exposure of cells had no effect on nucleotide synthesis. Some of t he problems encountered in the studies of purine and pyrimidine synthe sis are also discussed.