UZI GAFTER,TSIPORAMALACHI, YAACOV ORI, and HAIM BREITBART PETAH-TIKVA,TEL-AVIV,and RAMAT-GAN, ISRAEL
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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