Spontaneous DNA repair in human mononuclear cells is calcium-dependent

Spontaneous DNA repair in peripheral blood mononuclear cells (PBMC) has been recently described. The aim of this study was to evaluate whether spontaneous DNA repair is Ca²⁺-dependent, as in vitro-stimulated DNA repair. Spontaneous DNA repair in PBMC was measured in a 1 mM Ca²⁺ medium. The effect of extracellular Ca²⁺ chelation by EGTA, intracellular Ca²⁺ chelation by bapta-AM, and Ca²⁺ loading by the ionophore A23187 was examined. The signal transduction pathway was evaluated by inhibiting protein tyrosine kinase with genistein, calmodulin with W7, and calcineurin with cyclosporin A and tacrolimus. Extracellular Ca ²⁺ chelation had no effect on spontaneous DNA repair, while both intracellular chelation and calcium overloading inhibited the DNA repair. Inhibition of protein tyrosine kinase, calmodulin or calcineurin reduced DNA repair. In conclusion, spontaneous DNA repair is mainly Ca²⁺- dependent at a narrow range of intracellular Ca²⁺ concentrations. The signal transduction cascade includes protein tyrosine kinase, calmodulin, and calcineurin.