MIGRATION AND FATE OF CHARGES INITIALLY P RODUCED 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 wel l as in aqueous solution, can migrate along the DNA chain before being trapped. Electron migration distances are of the order of 100 base pa irs (the interbase pair distance being 3.4 Angstrom) in the first case , and about one order of magnitude smaller in the second case. Short-r ange hole migration processes seem to occur from the initial cation ra dicals 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 break s. The electrons produced during the ionization processes seem to reac t preferentially with the pyrimidine bases [cytosine (C) and thymine ( T)], with the formation of two anionic primary radicals, T--. and C--. . Based on thermodynamic and kinetic considerations about T--., it see ms that this latter is responsible for inducing single-strand breaks. When the electron is initially trapped by cytosine, a proton is transf erred to C--. from the complementary guanine. The deprotonation of thi s 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, loc ated at a distance equal to, or less than the characteristic electron migration distance. A pair of coupled free radicals, derived from cyto sine and guanine, namely, C(H)(.) and G(-H)(.), may thus be produced. The possible reactions between these two radicals could lead to: (i) t he reformation of C and G by recombination, (ii) the creation of an in terstrand covalent bond, and (iii) the induction of a double-strand br eak. These two latter processes may result in permanent damages of the DNA molecule. The deleterious effect of radiation on DNA is usually t hought to be the consequence of oxidation. However, according to the m echanism proposed here, it is interesting to note that the process lea ding to a double-strand break is initiated by an electron capture at a cytosine site, the oxidation process of the deprotonated complementar y base being a consequence of this capture.