Effects of anticonvulsant drugs on the synthesis of DNA and protein by human bone marrow cells in vitro.

Suspensions of human bone marrow cells were incubated with various concentrations of phenobarbitone or phenytoin sodium for 2 h, and the effects of this incubation on the subsequent incorporation of 3H-thymidine and3H-leucine into DNA and protein, respectively, were studied. Both drugs caused a depression of 3H-thymidine incorporation and this phenomenon was not prevented by the addition of 100 mug of pteroyl-glutamic acid, folinic acid or 5-methyltetrahydrofolate per ml of marrow culture. The lowest concentration of drug which caused a statistically significant depression of 3H-thymidine incorporation was 200 mug per ml for phenobarbitone and 50 mug per ml for phenytoin sodium. Both phenobarbitone and phenytoin sodium also caused an increase in the incorporation of 3H-leucine at concentrations of 50 and 20 mug per ml, respectively, suggesting the possibility that a stimulation of protein synthesis within erythropoietic cells may play an important role in the development of anticonvulsant-induced macrocytosis.