Migration of Electrons and Holes in Crystalline d(CGATCG)-Anthracycline Complexes X-Irradiated at 4 K.Michael T. Milano, Gary G. Hu, Loren D. Williams and William A. BernhardAbstract |
|
Electrons and holes generated in irradiated DNA migrate to stable trapping sites. Protonation and deprotonation reactions at these sites promote the trapping of electrons and holes, thereby inhibiting further migration. The extent of migration determines the final distribution of damage in irradiated DNA. In this study, electron and hole migration is investigated in a crystalline DNA hexamer, intercalated with an anthracycline drug. The intercalator is no further than two base pairs away from any DNA base.
From EPR measurements, there is no evidence of DNA centered radicals in the irradiated DNA hexamer. The aromatic region of the anthracycline intercalator evidently sequesters most or all of the electrons, and most of the holes. Further hole trapping and radical stabilization appears to occur on the anthracycline's amino sugar group, which is nestled in the minor groove of the hexamer. The relatively large yield of this proposed amino sugar radical suggests that holes, generated in the DNA solvation shell, migrate to the amino sugar where they become trapped. This would be the first observation of a radical, formed by the direct effect of low dose, low LET radiation, that is trapped within the DNA helix, yet lies outside of the stacked bases. With respect to holes generated in the DNA bases at 4 K, it is concluded that most, or all, are capable of migrating to an intercalator � 2 base pairs away. With respect to dry electrons, it is concluded that anthracycline effectively competes for electron trapping over a region of at least 2 base pairs; these experiments cannot distinguish between electron attachment to the bases followed by transfer to the intercalator versus direct attachment to the intercalator.
|
For reprint requests, contact:
Director of Molecular Biophysics & Structural Biochemistry Department of Biochemistry and Biophysics 601 Elmwood Avenue Rochester, NY 14642 |
