Lithium treatment prior to radiation exposure of human neuroblastoma cells modifies outcome of cellular damage

Abstract

Introduction: Radiation exposure to brain is known to cause cognitive deficits. Aim of the current study was to investigate whether lithium protects against radiation. It was further investigated whether this protective effect is associated with neuritogenesis and altered Neural Cell Adhesion Molecule (NCAM) expression. Materials and Methods: Human neuroblastoma cell line, SK-N-MC was exposed to gamma radiation alone and after 24 h pretreatment with lithium. Cells were scored for viability by MTT assay and checked for apoptotic changes by flow cytometry (FCM). Geimsa stained cells were scored for number of cells bearing neuritis and length of neuritis. Real time PCR was used to measure levels of NCAM transcript in the cells. Results: Radiation exposure of 5 Gray resulted in significant decrease in cell viability. Pretreatment with lithium rescued cells from radiation- induced toxicity as indicated by MTT assay and by FCM analysis. Morphological observations suggested radiation caused increase in neurite lengths and decrease in number of cells bearing neurites. This was reversed by lithium treatment. Several fold decrease in NCAM expression was observed post radiation exposure which was reversed by lithium pretreated cells. Conclusion: Lithium protects neuronal cells against radiation damage. The protective effect of lithium is associated with change in differentiation status of cells as indicated by neuritogenesis and with alteration in expression of NCAM, a molecule known to be associated with neurite formation.