Pulse Radiolytic Study of the Interaction of Thiols and Ascorbate with OH Adducts of dGMP and dG: Implications for DNA Repair Processes

Abstract

Using the technique of pulse radiolysis, the interaction of .OH radicals with 2''-deoxyguanosine (dG) and dG-5''-monophosphate (dGMP) results in the production of intermediates with different redox properties as demonstrated by their reactions with tetranitromethane (TNM) and N,N,N'',N''-tetramethyl-p-phenylenediamine. The ratio of the yields of oxidizing to reducing-type .OH radical adducts of dGMP was determined to be about 1:1 and independent of pH (6-11). The nature of the intermediates produced on reaction of .OH with dGMP are discussed. The thiols, cysteine, glutathione, mercaptoacetic acid and ascorbate interact with those .OH adducts of dGMP and dG with oxidizing properties preferentially via an electron transfer process (k .apprx. 3 .times. 107-1.4 .times. 109 dm3 mol-1 s-1) as implied from the pH dependence of the rate constants. Oxygen and TNM do not interact with those .OH adducts of the purines with oxidizing properties. The implicatioans of these findings are discussed with reference to the mechanistic aspects of radioprotection and especially of radiosensitization.