Mechanisms of Radiation‐Induced Strand Break Formation in DNA

The mechanisms by which γ‐radiation produces strand breaks in DNA were investigated using model systems: breakage of the sugar phosphate bond of deoxynucleotides irradiated in aqueous solution was equated to a reaction which would produce a strand break in DNA. Release of inorganic phosphate from 5′ deoxynucleotides is caused by a radiation‐produced hydroxyl radical abstracting a hydrogen atom from the deoxyribose moiety. Decay of the sugar radical so formed leads to phosphate release. After release of inorganic phosphate from deoxycytidylic acid two products are formed which consist of the cytosine base moiety attached to two or three carbon atoms of the sugar. Radioprotective sulphydryl compounds can repair the sugar radical by donation of a hydrogen atom to the damaged site. In thymidine 3′5′ diphosphate, reaction of OH* radicals with the base moiety as well as with the sugar can lead to inorganic phosphate release, both reactions leading to breakage of both 3′ and 5′ sugar phosphate bonds in the same molecule. When thymidine 3′5′ diphosphate is irradiated in the presence of oxygen, labile phosphate esters are produced in yields which are large compared to the inorganic phosphate yield. Reaction of 5‐bromouracil moieties in DNA with hydrated electrons can also lead to strand break production. Transfer of the electron to 5‐bromouracil from the thymine anion radical was found to be an efficient reaction. Other species such as HCO2−, O2−, and the cytosine anion radical can also donate electrons to 5‐bromouracil. The results and conclusions of these experiments are discussed with reference to reactions which could occur in DNA.