Effects of lonising radiation on deoxyribonucleic acid. Part 2. The influence of nitroimidazole drugs on the course of radiation damage to aqueous deoxyribonucleic acid

Abstract

Exposure of frozen aqueous solutions of calf-thymus DNA to ⁶⁰Co γ-irradiation at 77 K gave electron-gain centres localised on thymine (T^–) and electron-loss centres localised on guanine (G⁺), in approximately equal yields as judged from their e.s.r. spectra. The presence of metronidazole or misonidazole resulted in a marked reduction in the yield of T^–, the drug anions being detected in their place. The yield of G⁺ was not enhanced, in contrast to the results of others. Similar treatment of frozen aqueous solutions of plasmid DNA (pBR 322) was shown by gel electrophoresis to result in extensive single- and double-strand breaks in the absence of drug. Inclusion of metronidazole significantly reduced the number of strand breaks, double-strand breaks being reduced by a proportionately greater amount. An explanation is offered for this. At the molecular level these drugs clearly protect DNA from radiation damage (at least in terms of radical yield and strand breaks), despite the fact that they are known to be efficient radiosensitisers at the cellular level. These observations are discussed with regard to the various proposals for the mechanism of action of these drugs.