ELECTRON MIGRATION ALONG 5-BROMOURACIL-SUBSTITUTED DNA IRRADIATED IN SOLUTION AND IN CELLS

Solvated electrons generated in aqueous solution after exposure to ion izing radiation can be scavenged by DNA and then transferred along the DNA molecule. This mechanism of charge transfer provides an opportuni ty for radiation damage to be targeted to certain regions in the DNA m olecule and is a mechanism by which single-strand breaks contribute to locally multiply damaged sites to enhance cell lethality. Experiments were performed in which different amounts of 5-bromouracil (5-BrU) we re substituted for thymine in Escherichia coli DNA. The amount of brom ide released was assayed after quantitative reaction of radiation-indu ced solvated electrons with 5-BrU in DNA samples irradiated in solutio n and irradiated in the cellular environment. By varying the amount of 5-BrU incorporated in the DNA, the average distance between 5-BrU mol ecules was systematically changed and, because the number of 5-BrU/ele ctron reactions was monitored by the amount of bromine released, the m aximum average electron migration distance along the 5-BrU DNA could b e estimated. Using this approach, the maximum average electron migrati on distance in aqueous solutions of 5-BrU DNA was about 6.5 to 10 base distances in nonhybrid 5-BrU DNA (assuming only intrastrand migration ). Similar methods revealed charge migration in 5-BrU DNA incorporated into E. coli, and the maximum average migration distance was about 5 to 6 base distances (assuming only intrastrand migration). Only 11-16% of the electrons produced during radiolysis were scavenged by 5-BrU D NA in aqueous solution, and only 1% resulted in the release of bromide from 5-BrU-DNA inside E. coli.