Combination is the Dominant Free Radical Process Initiated in DNA by Ionizing Radiation: An Overview Based on Solid-state EPR Studies

Abstract

An overview of the early processes initiated in DNA by ionizing radiation is given from the perspective of studies done by solid-state EPR with the focus on radical combination. Comparisons with free radical formation and trapping in crystalline pyrimidines (1-methylcytosine, thymine, 1-methylthymine, 1-methyluracil, and cytosine monohydrate) provide insight into the processes occurring in DNA. Between 25 and 50% of low LET ionizations in fully hydrated DNA at 4K lead to trapped free radicals, the remaining unobserved radicals are assumed to have combined. The majority of the radicals trapped in DNA at 4K (G ∼ 0·3 µmol/J) are believed to be in clusters. Based on the value of G, it is argued that the range of holes and bound electrons in DNA at 4K are, in the main, limited to within the cluster diameter, ∼ 4 nm. Proton transfer across hydrogen bonds promotes radical trapping and inhibits combination but is thermally reversible. Warming to room temperature mobilizes the reversibly trapped radicals and gives additional combination (50–80% of those trapped at 4K). The yield of free radicals, after anneal, is sufficient to account for the yield of single-strand breaks produced by direct effects.