The role of calcium in human lymphocyte DNA repair ability.
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 environmental cause for genomal DNA damage is ultraviolet (UV) irradiation. The aims of the present study were (1) 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 Ca2+ homeostasis in these cells. UV-induced DNA repair ability in lymphocytes was maximal at 1 mmol/L CaCl2 in the medium. 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-(beta 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 cytosolic (Ca2+) elevation. These results emphasize the importance of a precise cellular Ca2+ 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.
Gafter
U
U
Department of Nephrology, Rabin Medical Center, Campus Golda, Petah-Tikva, Israel.
Malachi
T
T
Ori
Y
Y
Breitbart
H
H
D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology / Q000528:radiation effects; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D006706:Homeostasis / Q000528:radiation effects; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D007529:Isoflavones; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000252:Calcium-Transporting ATPases; D002118:Calcium