Abstract:
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 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 of the anthracycline intercalator evidently sequesters most or all of the 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 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, we conclude that most, if not all, are capable of migrating to an intercalator less than or equal to 2 base pairs away. With respect to dry electrons, we conclude that anthracycline competes effectively for electron trapping over a region of at least 2 base pairs; our experiments cannot distinguish between electron attachment to the bases followed by transfer to the intercalator and direct attachment to the intercalator. (C) 1998 by Radiation Research Society.

KeyWords Plus:
INDUCED DNA-DAMAGE, FREE-RADICAL YIELDS, AQUEOUS-SOLUTION, PULSE-RADIOLYSIS, PARAMAGNETIC-RESONANCE, SPIN-RESONANCE, NITROACRIDINE INTERCALATORS, COSTACKING COMPLEXES, REDUCTION POTENTIALS, RADIATION-DAMAGE

Addresses:
Bernhard WA, Univ Rochester, Dept Biochem and Biophys, 601 Elmwood Ave, Rochester, NY 14642 USA.
Univ Rochester, Dept Biochem and Biophys, Rochester, NY 14642 USA.
Georgia Inst Technol, Sch Chem and Biochem, Atlanta, GA 30332 USA.

Publisher:
RADIATION RESEARCH SOC, OAK BROOK

IDS Number:
ZV652

ISSN:
0033-7587