The Role of Endogenous Thiols in Intrinsic Radioprotection

Abstract

Observations are reviewed from experiments performed to study the role of endogenous thiols in the radiation response of cells using a glutathione-deficient and a related glutathione-proficient cell strain. The effect of glutathione in the initial radical reactions was considered and the yield of single-strand DNA breaks was the end-point of the response. The rejoining of breaks and clonogenic survival were chosen as end-points when, in addition, the role of glutathione in the subsequent biochemical processes was studied. The results were interpreted to indicate that glutathione plays a role in both the radical and the biochemical reactions which follow irradiation. In the former case, it functions as a damage-restituting reactant, in general agreement with the 'competition model'. Some biochemical repair processes, in particular those concerned with the rejoining of breaks induced by radiation in the presence of oxygen or misonidazole, appear also to be critically dependent on glutathione. Due, probably, to its particular spatial distribution, endogenous glutathione is specific in the radical processes, and exogenous thiols cannot be substituted for it. No such specificity was indicated in the biochemical processes related to strand break rejoining.