Free Radical Reactions with DNA

The -N02 radical (and also the C03 radical) are of some biological interest (Augusto et al. 2002) because they play some role in the reactions of peroxyni-trite (Chap. 2.4). For example, "N02 oxidizes tyrosine to nitrotyrosine (Prutz et al. 1985b), and the latter has been considered a promoter of free-radical damage in DNA model systems (Prutz 1986). In this context, it may be of interest that CCV reacts with a self-complementary ODN (k = 1.9 x 107 dm3 mol-1 s 1) exclusively at G (by ET) (Chap. 11.2). 

NEM and also diethylmaleate (DEM) reduce the GSH content of cells by binding (Bump et al. 1982), but other reaction pathways have been considered as well (Mullenger and Ormerod 1969). NEM, for example, is also effective when given shortly after irradiation (Han et al. 1976) pointing to an interference with the enzymatic repair rather than at the level of free-radical reactions. The reactions with DNA radicals is too slow to be of any marked effect (Simic and Hayon 1971 Hayon and Simic 1972). 

The frequency with which two reactive species encounter one another in solution represents an upper bound on the bimolecular reaction rate. When this encounter frequency is rate limiting, the reaction is said to be diffusion controlled. Diffusion controlled reactions play an important role in a number of areas of chemistry, including nucleation, polymer and colloid growth, ionic and free radical reactions, DNA recognition and binding, and enzyme catalysis. 

The use of gaseous tritiated radical scavengers to determine the secondary free radical distribution in y-irradiated lyo-philized macromolecules has been explored. For proteins the similarity of the tritium distributions obtained with tritiated H2S and HI as well as studies with H235S, support the assumption that these distributions are an approximate measure of the secondary radical distribution. Radical distributions of several native proteins were characteristically different, those of denatured proteins approximately the same, thus demonstrating a pronounced effect of conformation. In contrast to proteins, the reaction of irradiated dry DNA with tritiated H2S or HI gave approximately 100 times more tritium label on the DNA than expected from the initial concentration of free radicals in the DNA. 

---