Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344)

Gap junction channels maintain cell-cell communication and are essential fo r the coordination of tissues, playing a pivotal role in embryonal developm ent. Gap junctional intercellular communication (GJIC), studied here in hum an fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F34 4), was almost doubled upon exposure to thalidomide (10 muM) in the presenc e of NADH or NADPH (20 muM). Neither in HFFF2 nor in WB-F344 cells did any detectable alteration in GJIC occur with the thalidomide analog EM 16 (10 m uM), known as a non-teratogenic compound. The thalidomide analog EM 364 (10 muM) increased GJIC without prior metabolic activation. It is suggested th at GJIC modification may be related to the pharmacological and toxicologica l properties of thalidomide. (C) 2001 Elsevier Science Inc. All rights rese rved.