Migration and fate of charges initially produced in irradiated DNA: a review

It has been shown that the charges, electrons and 'holes', generated by the action of ionizing radiation on DNA, in the solid phase as well as in aqueous solution, can migrate along the DNA chain before being trapped. Electron migration distances are of the order of 100 base pairs (the inter-base pair distance being 3.4 A) in the first case, and about one order of magnitude smaller in the second case. Short-range hole migration processes seem to occur from the initial cation radicals to sites located predominantly at the purine bases [adenine (A) and guanine (G)], with guanine being the most favorable hole trapping center. This radical cation G+. may undergo charge recombination or lead to a reaction sequence susceptible to induce single-strand breaks. The electrons produced during the ionization processes seem to react preferentially with the pyrimidine bases [cytosine (C) and thymine (T)], with the formation of two anionic primary radicals, T-.. Based on thermodynamic and kinetic considerations about T-., it seems that this latter is responsible for inducing single-strand breaks. When the electron is initially trapped by cytosine, a proton is transferred to C-. from the complementary guanine. The deprotonation of this guanine leads to a reduction potential decrease of 200 mV, creating an electron donor site G(-H)-. This site is susceptible to transfer an electron to a radical cation, or to its subsequent intermediates, located at a distance equal to, or less than the characteristic electron migration distance. A pair of coupled free radicals, derived from cytosine and guanine, namely, C(H). and g(-H)., may thus be produced. The possible reactions between these two radicals could lead to: (i) the reformation of C and G by recombination, (ii) the reaction of an interstrand covalent bond, and (iii) the induction of a double-strand break. These two latter processes may result in permanent damages of the DNA molecule. (authors). 97 refs., 6 figs., 3 tabs