The contribution of hydroxyl radical to radiosensitization: a study of DNA damage

Using the radioprotector dimethylsulfoxide, DMSO, as a scavenger of hydroxyl radicals, the proportions of DNA damage caused by OH. were determined in mammalian cells irradiated in hypoxia with or without the radiosensitizers misonidazole and TAN or in air. Yields of both single-strand breaks (SSB) and base/sugar damage (MLS for Micrococcus luteus sensitive sites) were measured for each situation. Most of the damage enhanced by the sensitizers was found to be OH. dependent, for both MLS and SSB classes of damage: most breaks (greater than 80%) enhanced by oxygen and about two-thirds of the breaks enhanced by misonidazole (hypoxia) occur at OH.-damaged sites; most if not all base/sugar damage enhanced by the sensitizers misonidazole and TAN (in hypoxia) occurs only in the presence of OH., whereas in air, some (about one-quarter) of the enhanced MLS damage does not require OH.. The sensitizer enhancement ratios in the presence of scavenger and the degree of protection afforded by the scavenger determined for total (MLS + SSB) damage agree well with those derived from corresponding survival experiments.