Phenytoin-induced DNA synthesis and inositol 1,4,5-trisphosphate formation in L-929 fibroblasts.

Culture of L-929 fibroblasts in the presence of phenytoin (2.5-5.0 micrograms/ml) increased DNA synthesis, as indicated by increased [3H]thymidine uptake, while a higher dose (20 micrograms/ml) inhibited DNA synthesis. In like manner, a low dose of phenytoin (5.0 micrograms/ml) was effective in increasing inositol 1,4,5-trisphosphate formation while a higher dose (10 micrograms/ml) tended to inhibit this activity. These data suggest that the formation of inositol phosphate second messengers may play a role in phenytoin-induced fibroblast proliferation and connective tissue growth.