Oxidative DNA Damage and Repair in Rat Kidney

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9631166 Gallagher A number of chemical reactions occur in cells affected by the loss of oxygen and by reoxygenation which occurs upon resumption of blood flow. One by-product of these cellular reactions is the formation of a highly reactive form of oxygen, known as an oxygen free radical. Oxygen free radicals produce alterations in DNA, the genetic material, which may affect the ability of cells to carry out their normal biological functions. Since a single change in DNA structure may be harmful, it is not surprising that a diverse array of mechanisms for repairing DNA evolved at the cellular level. The experiments outlined in this proposal are designed to examine an enzyme, redoxyendonuclease, that repairs oxidative damage to DNA. The levels of this enzyme will be quantified in the oxygen-deprived (ischemic) kidney and the reoxygenated reperfused) rat kidney and compared to the levels of this protein in the undamaged tissue. Specifically, the tissue will be examined for 1) the level of the oxidative DNA repair enzyme activity; 2) the cellular repair of oxidized DNA damage; and 3) the levels of specific oxidized DNA base damages formed during the ischemic or reoxygenanon event. Results from these experiments will provide new insights into the regulation of the cellular mechanisms that repair oxidative DNA damage and the ability of tissues to withstand conditions of oxidant stress.