Studies on Agranulocytosis. IV. Effects of Chlorpromazine on Nucleic Acid Synthesis of Bone Marrow Cells in Vitro

1. When viable marrow cells were incubated with tritiated thymidine and uridine, the cells became radioactive as nucleic acid synthesis proceeded.

2. Excessive concentrations of chlorpromazine (CPZ) partially inhibited the influx of thymidine and uridine into granulocytes of all patients who had had agranulocytosis due to this drug, and of about 75 per cent of random hospital patients. This drug did not effect nucleic acid synthesis in nine individuals who had been treated with a large amount of CPZ, with no alteration in their leukocyte count.

3. A comparison of the effects of dilution of CPZ upon influx of H³ thymidine into granulocytes showed significant dose-dependent depression of granulocyte labeling in CPZ sensitive persons, and no depression in granulocytes of persons on large doses of CPZ who did not develop leukopenia. Random hospital patients not on CPZ showed a degree of depression between these two groups.

4. The number of radioactive normoblasts in the marrow culture preparations diminished slightly, but not significantly, following incubation with CPZ.

5. Non-myelotoxic drugs, such as Phenergan, aspirin, penicillin, and tetracyclene had no significant effect on the degree of influx of tritated thymidine and uridine.

6. There was no effect of CPZ upon incorporation of H³ DL-leucine into marrow cells.