Radiolytic Pathways in γ-Irradiated DNA: Influence of Chemical and Conformational Factors

Several chemical and conformational factors have been shown to interfere with the radiolytic pathways in γ-irradiated DNA, producing different radical populations on the macromolecule. These factors include anoxic or oxic conditions, relative hydration degree, denaturation and/or degradation, and base composition. This led to extreme variations in the ESR spectra. Nevertheless, computer-assisted analysis of these spectra revealed the following common composition: a doublet from thymine anions ($\dot{{\rm T}}^{-}$), a singlet from guanine cations ($\dot{{\rm G}}^{+}$), an octet from 5-thymyl radicals (ṪH), and an asymmetrical doublet from thymine-located peroxyl radicals (TOȮ). This formal interpretation of the experimental spectra permitted us to elucidate the following basic features for DNA radiolysis in frozen aqueous solution: -Neutral DNA solutions frozen at 77 K are phase-separated systems. Radiation damage to DNA does not result from the indirect effects of radiation. -Primary radicals on DNA are ions of both signs, randomly produced on the constituent bases. -Charge migration occurs via the stacked bases. Thymine is the eventual sink of the long-range electron migration. Guanine is the eventual sink of the short-range positive hole migration. Migration phenomena may be partially or totally hindered by various interfering factors. -With increase in temperature, ionic radicals enter conversion reactions: $\dot{{\rm G}}^{+}$ decays without reacting with the surrounding water molecules, whereas $\dot{{\rm T}}^{-}$ does react to form the 5-thymyl radical. -In the presence of oxygen, peroxyl radicals TOȮ are formed rather than 5-thymyl radicals. -No sugar-located free radicals have been detected in the course of the present investigation.