THE ROLE OF CALCIUM IN HUMAN LYMPHOCYTE DNA-REPAIR ABILITY

DNA repair ability is reduced in a variety of pathologic conditions. I n addition, in some of these diseases a disturbance in cellular Ca hom eostasis occurs or cytosolic (Ca2+) responses to various stimuli are i mpaired. The leading environmental cause for genomal DNA damage is ult raviolet (UV) irradiation. The aims of the present study were (1) to e valuate a possible dependence of UV-induced DNA repair ability on cyto solic Ca2+ in human lymphocytes and (2) to assess the direct effect of UV irradiation on Ca2+ homeostasis in these cells. UV-induced DNA rep air ability in lymphocytes was maximal at 1 mmol/L CaCl2 in the medium . Suppression of DNA repair ability occurred after elevation or reduct ion of cellular (Ca2+) when various methods were used, including chang es in Ca2+ concentration in the medium, cellular Ca2+ depletion by eth yleneglycol-bis-(beta aminoethylether)-N,N,N',N'-tetraacetic acid, exc essive Ca2+ concentration induced by ionophore, and shortening of Ca2 presence time during repair synthesis. UV irradiation caused an immed iate and significant rise in cytosolic (Ca2+) that was the result of b oth enhanced Ca2+ uptake and inhibition of plasma membrane Ca-adenosin e triphosphatase activity. The tyrosine kinase inhibitor genistein inh ibited both UV-induced DNA repair and UV-induced cytosolic (Ca2+) elev ation. These results emphasize the importance of a precise cellular Ca 2+ level regulation for the optimal DNA repair process. UV irradiation , by inducing cellular Ca2+ rise, may activate DNA repair as soon as D NA is damaged.