ELECTRON-SPIN-RESONANCE STUDIES OF RADIATION-DAMAGE TO DNA AND TO PROTEINS

Exposure of biopolymers to ionising radiation in dilute aqueous solution results in damage to water and the resulting radicals attack the solute molecules in various ways. This form of damage is usually described as ''indirect''. However, in cellular systems ''direct'' damage is more frequent, especially to nuclear DNA, where the concentration of water may be quite low. In this review, I am primarily concerned with direct damage. The initial chemical consequence of direct damage is electron-ejection followed by electron-capture. ESR studies have established that electron-loss is fixed in the purine bases (mainly as G-(+)) whilst electron-capture occurs mainly at the pyrimidine bases (C-(-) and T-(-)). Almost certainly, these centres are stabilized by proton-loss and proton-gain. These results indicate that even though electron-loss must occur initially from all regions of the DNA, including the phosphate and sugar units, it moves rapidly into the stacked base system. Similarly, the ejected electrons fail to react with phosphate and react preferentially with the bases. Also, the electron-hole and electron-gain centres are well separated, since radical-pairs (triplet-states) have never been detected by ESR spectroscopy. A similar situation arises for direct damage to proteins. Electron-loss must initially be mainly from the amide backbone and the ESR results suggest that this is rapidly trapped by loss of an N-H proton to give amido radicals. However, electrons are not trapped by the protein backbone, unless there are no electron-affinic groups present. In many cases, the results establish that these electrons move through large distances before being specifically trapped at unique sites.