The oxygen effect in permeabilized and histone-depleted cells: An enhanced OER for DNA double-strand breaks, compared to single-strand breaks, is abolished by soluble scavengers

Abstract

. The oxygen enhancement ratios (OER) in mammalian cells for DNA single- and double-strand breaks (ssb and dsb) are similar, usually 2-3. This seems to contradict the hypothesis that dsb are formed by multiple lesions, since one would then expect a quadratic OER for dsb compared to ssb. A higher OER for dsb than for ssb was however found in permeabilized cells (OERdsb=7.7; OERssb=4.3) and histone-depleted cells (OERdsb=20; OERssb=2.3), in the presence of an SH-compound, mercaptoethylamine. This higher OER could be counteracted by addition of the OH-radical scavenger DMSO. The OERdsb /OERssb ratio thus increases when the indirect effects increase. The repair of directly induced DNA lesions by hydrogen donation seems to be less efficient than the repair of indirectly induced lesions. It is suggested that differences in the fraction of unrepairable breaks differs for ssb and dsb and that this is the reason for the non-quadratic OERdsb compared to OERbssb found in cells. In the absence of SH-compounds, there was no oxygen effect for ssb in permeabilized and histone depleted cells. In contrast to this, a small oxygen effect was observed for dsb in permeabilized cells and this effect increased after histone depletion, reaching a value of OER=1.8. This oxygen effect seems to be linked to generation of dsb by single OH radicals.