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The role of calcium in human lymphocyte DNA repair ability

By May 1, 2018DNA Repair

The role of calcium in human lymphocyte DNA repair ability

Uzi Gafter,Tsipora Malachi, Yaacov Ori, and Haim Breitbart

DNA repair ability is reduced in a variety of pathologic conditions. In addition, in some of these diseases a disturbance in cellular Ca homeostasis occurs or cytosolic [Ca2÷] responses to various stimuli are impaired. The leading environ- mental cause for genomal DNA damage is ultraviolet (UV) irradiation. The aims of the present study were (I) to evaluate a possible dependence of UV-induced DNA repair ability on cytosolic Ca2÷ in human lymphocytes and (2) to assess the direct effect of UV irradiation on Ca 2÷ homeostasis in these cells. UV-induced DNA repair ability in lymphocytes was maximal at I mmol/L CaCI2 in the me- dium. Suppression of DNA repair ability occurred after elevation or reduction of cellular [Ca2÷] when various methods were used, including changes in Ca2÷ concentration in the medium, cellular Ca2÷ depletion by ethyleneglycol-bis- (l~aminoethylether)-N,N,N’,N’-tetraacetic acid, excessive Ca2+ concentration induced by ionophore, and shortening of Ca2÷ presence time during repair synthesis. UV irradiation caused an immediate and significant rise in cytosolic [Ca2÷] that was the result of both enhanced Ca2÷ uptake and inhibition of plasma membrane Ca-adenosine triphosphatase activity. The tyrosine kinase inhibitor genistein inhibited both UV-induced DNA repair and UV-induced cyto- solic [Ca2÷] elevation. 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 DNA is damaged. (J Lab Clin Med 1997;130:33-41)

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