The Contribution of Hydroxyl Radical to Radiosensitization: A Study of DNA Damage

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Abstract
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 [2,2,6,6-tetramethyl-1,4-piperidone-N-oxyl] 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 (> 80%) enhanced by O2 and .apprx. 2/3 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 (.apprx. 1/4) 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.

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