Model Studies for the Direct Effect of High-energy Irradiation on DNA. Mechanism of Strand Break Formation Induced by Laser Photoionization of Poly U in Aqueous Solution

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Abstract
Laser flash photolysis of polyuridylic acid (poly U) in anoxic aqueous solutions leads to biphotonic photoionization of the uracil moiety followed by the formation of single strand breaks (ssb). The rate constant for ssb formation (1·0 s−1, obtained from the slow component of conductivity increase at 23°C and pH 6·8) increases with decreasing pH to 235 s−1 at pH 3·5. The activation energy (pre-exponential factor) was measured to be 66 kJ mol−1 (5 × 1011 s−1) at pH 6·8. Addition of dithiothreitol (DTT) or glutathione (GSH) prevents ssb formation by reacting with a poly U intermediate (rate constant = 1·2 × 106 and 0·16 × 106 dm3 mol−1 s−1, respectively). Since with OH radicals as initiators very similar data have been obtained for the kinetics of ssb formation and for the reaction with DTT, we conclude that photoionization of the uracil moiety in poly U leads eventually to the same chemical pathway for ssb formation as that induced by OH radicals. Furthermore, we propose that protection by DTT and GSH occurs via H donation to the C-4′ radicals of the sugar moiety of DNA and to the C-4′ and the C-2′ radicals of poly U.

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