‘Chemical Repair’ in Irradiated DNA Solutions Containing Thiols and/or Disulphides. Further Evidence for Disulphide Radical Anions Acting as Electron Donors

Summary

The ring-closed disulphide radical anion D/SS^{· −}, formed radiolytically either by hydrogen abstraction from dithiothreitol (D(SH)₂), or by one-electron reduction of the corresponding cyclic dithiane (DS₂), is proposed to engage efficiently in ‘chemical repair’ of ^·OH-induced DNA intermediates (DNA^·) under gamma-irradiation of aqueous DNA solutions, Evidence for this concept derives from the observation that radioprotection of DNA by DS₂ or D(SH)₂ can be enhanced in anoxic N₂O-saturated solution by the addition of formate, at a constant total ^·OH scavenger capacity: carbon dioxide radical anions (CO^{· −}₂) actually promote the generation of D/SS^{· −}, by interacting both with DS₂ and D(SH)₂. Oxygen enhancement of radiation-induced DNA damage in systems containing DS₂ and/or D(SH)₂ can be easily explained with the above concept, as previously proposed in the case of cysteine (Prütz and Mönig 1987), by O₂-induced annihilation of the protective disulphide radical anion. In further support of the mechanism proposed it is shown that the protection efficiency under anoxia, and concomitantly the oxygen enhancement, increase with dose rate and with salt concentration, when DNA is irradiated in presence of DS₂.