Toxic effects of antiepileptic drugs on immunoglobulin gene expression

Murine myeloma cells were exposed to toxic, growth-retarding levels of two antiepileptic drugs (AEDs2), phenytoin (PHT) and carbamazepine (CBZ). J558L cells were treated for 12 days, washed free of drug and, upon recovery of growth, cloned to determine the frequency of lambda light chain secreting lines. Our results indicate that short-term exposure to high, toxic levels (5-10 times the therapeutic dose) of PHT and CBZ reduces or eliminates lambda light chain secretion at a high frequency. Furthermore, although most cloned lines tested positive for cytoplasmic lambda light chain, some lines had no detectable cytoplasmic immunoglobulin (Ig). The data are consistent with the hypothesis that long-term changes in fully differentiated B cell function may occur after toxic level AED exposure.