Hydrogen peroxide protects yeast cells from inactivation by ionizing radiation: a radiobiological paradox.

ABSTRACT

PURPOSE: To elucidate mechanisms of the interaction of hydrogen peroxide with chloride-derived cytotoxins under steady-state irradiation conditions and to determine the effects on cell viability. MATERIALS AND METHODS: Yeast cells were suspended in phosphate-buffered saline and exposed to 60Co gamma-irradiation under different conditions. The colony-forming ability was determined. RESULTS: Irradiation of PBS produces H2O2 and HOCl simultaneously. Under slightly acidic conditions and low oxygen tension the yield of HOCl exceeds that of H2O2 while at physiological pH and normoxic conditions H2O2 exceeds HOCl. Both substances react with each other rapidly in a pH-dependent way, even during an irradiation that lasts several seconds. As HOCl is about 1000-fold more toxic than H2O2 to the strain of Saccharomyces cerevisiae used in these experiments, it is evident that in an irradiation that produces more HOCl than H2O2 the radiation-induced damage will be large. If, in contrast, the cells are irradiated under conditions in which H2O2 production predominates, the damage will be small. One would therefore predict that addition of hydrogen peroxide to a cell suspension prior to irradiation should result in protection for suspended cells if H2O2 interferes with the generation of HOCl and thereby inactivates this more powerful toxin. Our data show that addition of H2O2 in sublethal concentration decreases radiation-induced cell death to the level that is found in chloride-free solution, i.e. depending on pH, reduces it by a factor of > or = 3.