RETINOIC ACID DIFFERENTIATED SH-SY5Y HUMAN NEUROBLASTOMA-CELLS - AN IN-VITRO MODEL TO ASSESS DRUG NEUROTOXICITY

Purpose: To evaluate whether retinoic acid (RA) differentiated human n euroblastoma (HN) SH-SY5Y cells are a suitable and reliable model to t est the neurotoxicity of chemotherapic drugs without the confusing eff ects of the neurotrophic factors commonly used to induce neuronal diff erentiation. Methods: Cultures of the SH-SY5Y cell line were exposed t o RA to induce neuronal differentiation which was assessed by measurin g the neurite length. The effect of increasing concentrations of cispl atin (CDDP) on neurite outgrowth was determined Cyclophosphamide (CTX) was used as negative control Results: CDDP induced a significant redu ction in the mean neurite length in a dose dependent manner. The neuro toxic effect of CDDP was reversible. Cyclophosphamide did not induce c hanges in RA differentiated HN cells. Conclusions: RA differentiated H N cells are sensitive to the neurotoxic effect of CDDP and the course of the changes is similar to that observed in clinical practice and in in vivo experimental models Therefore, this model is proposed as a sc reening method to test the neurotoxicity of chemotherapy drugs and the possible effect of neuroprotectant molecules and drugs.