HYDROXYL RADICAL-INDUCED DAMAGE TO THE PURINE-BASES OF DNA - INVITRO STUDIES

The hydroxyl (OH.) radical plays an important role in the degradation of living tissues induced by ionizing radiation. One of the main cause s of this phenomenon are the chemical changes in the DNA bases produce d by the reaction with this radical. A general comparison is made conc erning the reaction of the OH. radical with the two purine bases of DN A. The results obtained for adenine and guanosine and their derivative s are based on time resolved studies (by pulse radiolysis with optical and conductance detection) of the primary radicals formed and their t ransformation reactions, and on identification (by HPLC with UV and el ectrochemical detection) of the corresponding final products. The OH. radical reacts with adenine and guanine (and also with their nucleosid es, nucleotides and methylated derivatives) by addition to C(4), C(5) and C(8). The corresponding adducts undergo first order transformation s, identified as dehydration and opening of the imidazole ring, which can be distinguished by their different activation parameters and sens itivity to acid-base catalysis. The resultant radicals are characteriz ed by their different redox properties enabling the establishment of a mass balance that accounts quantitatively for the fate of the OH. rad ical. The analysis of stable products shows that some radicals are rep aired to the parent compound and others lead to structurally modified products. The hydroxylation at C(8) is an example of the latter, and a biologically relevant phenomenon.