EFFECT OF CULTURE AGE ON THE SUSCEPTIBILITY OF DIFFERENTIATING NEUROBLASTOMA-CELLS TO RETINOID CYTOTOXICITY

The cytotoxic effects of retinoids on neuroblastoma cells at various t imes during electrophysiological differentiation were evaluated. We us ed N1E-115, a clone of the murine neuroblastoma C1300 derived from the neural crest, and three retinoids: vitamin A (retinol), all-trans ret inoic acid (tretinoin), and 13-cis-retinoic acid (isotretinoin). Diffe rentiating N1E-115 cells exposed to retinoids at an isotretinoin EC(50 ) of 16 mu M exhibited the greatest vulnerability in terms of cell dea th during a period (8 to 10 days) that was previously found to be the most sensitive for induction of gross malformations in rodents. This f inding suggested possible similarities between the in vivo and in vitr o retinoid mechanism(s) of action. The greatest period of vulnerabilit y to retinoid cytotoxicity was also found to coincide with the rapid r esting membrane potential (V-m) development period, suggesting a linka ge between neuronal V-m and/or electrical excitability development and vulnerability to retinoid cytotoxicity. (C) 1996 John Wiley & Sons, I nc.