MECHANISMS OF OXYGEN RADIOSENSITIZATION IN IRRADIATED YEAST .1. DNA DOUBLE-STRAND BREAKAGE

The relative contributions of the OH-mediated and direct radiation eff ect 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 a n 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 attribut ed to the OH-mediated (or indirect) radiation effect, whereas in hypox ic cells the indirect effect is only about 45%. High oxygen enhancemen t ratios (OERs) are observed for the OH-mediated radiation effect (4.2 4 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 an d indirect) OER is 2.74 (GSH+) and 2.03 (gsh-). The dependence of radi osensitization for double-strand breakage on oxygen concentration is c haracterized by three components whose K-values are 0.5, 4 and 20% oxy gen for GSH+ cells and 0.45, 5 and 60% oxygen for gsh- cells. Evidence is presented that the first two components represent the radiosensiti zation by oxygen of the OH-mediated effect, whereas the third componen t, requiring the highest oxygen concentration for sensitization, repre sents the radiosensitization by the direct effect. GSH+ and gsh- cells show virtually the same K-values for the OH-mediated effect, but diff erent K-values for the direct effect.