Effect of antiepileptic drugs on growth of murine lymphoid tumor cells in single-cell culture.

The effect of three commonly used antiepileptic drugs (AEDs), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), on the growth of lymphoid tumor cells was assessed in vitro. A single-cell culture method was used to determine growth rates by direct visualization. The amount of free drug was determined by ultrafiltration to ascertain its correlation to therapeutic drug levels. VPA slowed the growth of B-myeloma (FO) and T-lymphoma (AKR-1) cells significantly within the range of therapeutic drug levels. CBZ and PHT likewise inhibited cell growth in both lineages but at two to four times the therapeutic level of free drug. CBZ was shown to have long-term effects on FO and AKR-1 cells, demonstrated by the reduced growth rates of cloned lines for 2-3 months after drug removal. Cloned sublines of myeloma cells secreting lambda light chain (J558L) treated with CBZ or PHT had a higher frequency of lambda light chain secretion loss mutations than the nontreated parent line.