Toxic Effects of Antiepileptic Drugs on Immunoglobulin Gene Expression

Abstract

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 λ 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 λ light chain secretion at a high frequency. Furthermore, although most cloned lines tested positive for cytoplasmic λ 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.