Exposure of aqueous solutions of DNA to 60Co γ-rays at 77 K gave radicals whose e.s.r. spectra suggest the presence of guanine cations (G˙+) and thymine anions (T˙–) in about equal yield. Hydroxyl radicals, also detected, were shown to be entirely confined to the pure ice phase, and are not involved in reactions with DNA. The fate of these radicals in the presence and absence of oxygen is discussed, and it is shown by strand-break analysis that there is a significant set of reactions leading to strand-breaks originating both from G˙+ and T˙–. The relatively high proportion of double strand-breaks is explained in terms of pairwise trapping of G˙+ and T˙–. When various electron-affinic compounds are added and the systems frozen, they selectively trap electrons, with consequent loss of T˙–, and its protonated product, ˙TH. Compounds such as nitroimidazoles, which from stable anions, appear to protect DNA, and there is an appreciable fall in the number of strand-breaks. Others, such as iodoacetamide or hydrogen peroxide decrease the yields of T˙– and ˙TH, but the reactive products, ˙OH and H2ĊCONH2, react with DNA so that there is little net change in total damage. Attack by ˙OH is facile, and results in the formation of several carbon-centred radicals which are thought to be formed by hydrogen abstraction from the sugar units. However, there is no major increase in the number of strand-breaks under these conditions. Disulphides also act as efficient electron traps and hence as radio-protecting agents. Sulphydryl compounds, RSH, such as glutathione, do not react initially, but on annealing, the concentration of DNA radicals falls and RSSR– radical anions are detected. The number of strand-breaks is thereby greatly diminished. These results strongly support the theory that RSH compounds are important repair agents for DNA. Compounds such as intercalators and transition-metal complexes which bind directly to DNA are even more efficient at diverting damage to themselves, probably at the electron-transfer level. However, these are not likely to be suitable as radiation protection agents. The properties thought to be desirable for such agents are briefly discussed. Finally, attention is turned to the effect of radiation on DNA–histone complexes and on chromatin. The results are remarkable in that they establish efficient transfer of electrons generated in the proteins to DNA, giving enhanced yields of T˙– and ˙TH. In contrast, the histone hole-centres do not appear to migrate in this way.
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