Mechanisms of Oxygen Radiosensitization in Irradiated Yeast

Abstract

The relative contributions of the OH-mediated and direct radiation effect on the induction of DNA double-strand breaks (dsbs) were evaluated in two haploid yeast cell lines (GSH⁺ and gsh⁻) irradiated under oxic or hypoxic conditions in the absence or presence of 6 m glycerol as an OH radical scavenger. Gsh⁻ cells are deficient in glutathione (GSH) biosynthesis, their GSH content is only 2% compared with GSH⁺ cells. Similar relative contributions are observed for both cell lines. Under oxic irradiation conditions about 64% of the response can be attributed to the OH-mediated (or indirect) radiation effect, whereas in hypoxic cells the indirect effect is only about 45%. High oxygen enhancement ratios (OERs) are observed for the OH-mediated radiation effect (4·24 for GSH⁺, 2·70 for gsh⁻ cells) and low OERs for the direct effect (1·66 for GSH⁺, 1·44 for gsh⁻ cells). The weighted total (i.e. direct and indirect) OER is 2·74 (GSH⁺) and 2·03 (gsh⁻). The dependence of radiosensitization for double-strand breakage on oxygen concentration is characterized by three components whose K-values are 0·5, 4 and 20% oxygen for GSH⁺ cells and 0·45, 5 and 60% oxygen for gsh⁻ cells. Evidence is presented that the first two components represent the radiosensitization by oxygen of the OH-mediated effect, whereas the third component, requiring the highest oxygen concentration for sensitization, represents the radiosensitization by the direct effect. GSH⁺ and gsh⁻ cells show virtually the same K-values for the OH-mediated effect, but different K-values for the direct effect.