MODIFICATION OF THE REDUCTIVE PATHWAY IN GAMMA-IRRADIATED DNA BY ELECTRON SCAVENGERS - TARGETING THE SUGAR-PHOSPHATE BACKBONE

Several electron scavengers that irreversibly form potential hydrogen- abstracting species upon one-electron reduction have been tested as ag ents for conversion of reductive damage to DNA bases into damage to th e sugar-phosphate backbone. Electron spin resonance spectroscopy is em ployed to follow the production of radicals and transformations after irradiation. The scavengers tested included neutral (acrylamide, iodoa cetamide) and cationic [triphenylsulfonium (Ph3S+), o,o'-diphenylenebr omonium (DPB) and o,o'-diphenyleneiodonium (DPI)] compounds. Modificat ion of reductive radiation damage in DNA is found to occur by scavengi ng of initial mobile electrons at low temperatures as well as thermall y activated electron transfer from DNA electron-gain centers upon anne aling. Electron transfer from the bases to hydrogen-bonded acrylamide has the smallest activation energy among other scavengers but produces a secondary alkyl radical incapable of abstracting hydrogen from the sugar-phosphate backbone. A primary alkyl radical generated from iodoa cetamide has been shown to abstract preferentially from the thymine me thyl group but not from deoxyribose moieties. Aryl radicals generated from aromatic onium salts such as Ph3S+, and especially DPI and DPB, a re found to be the agents which best abstract hydrogen atoms from the deoxyribose portion of DNA. The use of DPB and DPI as radiation modifi ers allows the elimination of undesirable side reactions of aryl radic als and through hydrogen abstraction results in high yields of a speci es identified as the DNA Cl'(.) sugar radical. The second reaction pat hway found for DPI and DPB in DNA is addition of an aryl radical to th e thymine 5,6 double bond. Cysteamine is shown to preferentially elimi nate sugar radicals upon annealing and to have little impact on the th ermal stability of the thymine adduct radical. (C) 1998 by Radiation R esearch Society.