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Neuroblastoma is the most recurring cancer in childhood and adolescence. The SH-SY5Y neuroblastoma cell line is generally adopted for elaborating new therapeutical approaches and/or elaborating strategies for the prevention of central nervous system disturbances. In fact, it represents a valid model system for investigating in vitro the effects on the brain of X-ray exposure using vibrational spectroscopies that can detect early radiation-induced molecular alterations of potential clinical usefulness. In recent years, we dedicated significant efforts in the use of Fourier-transform and Raman microspectroscopy techniques for characterizing such radiation-induced effects on SH-SY5Y cells by examining the contributions from different cell components (DNA, proteins, lipids, and carbohydrates) to the vibrational spectra. In this review, we aim at revising and comparing the main results of our studies to provide a wide …