MIGRATION OF ELECTRONS AND HOLES IN CRYSTALLINE D(CGATCG)-ANTHRACYCLINE COMPLEXES X-IRRADIATED AT 4 K

Electrons and holes generated in irradiated DNA migrate to stable trap ping sites. Protonation and deprotonation reactions at these sites pro mote the trapping of electrons and holes, thereby inhibiting further m igration. 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 anth racycline drug. The intercalator is no further than 2 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 o f the anthracycline intercalator evidently sequesters most or all of t he electrons and most of the holes. Further hole trapping and radical stabilization appear 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 g enerated 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 tra pped within the DNA helix, yet lies outside of the stacked bases. With respect to holes generated in the DNA bases at 4 K, we conclude that most, if not all, are capable of migrating to an intercalator less tha n or equal to 2 base pairs away. With respect to dry electrons, we con clude that anthracycline competes effectively for electron trapping ov er a region of at least 2 base pairs; our experiments cannot distingui sh between electron attachment to the bases followed by transfer to th e intercalator and direct attachment to the intercalator. (C) 1998 by Radiation Research Society.