Radiosensitization of Escherichia coli by Methyl Hydrazine and the Effect of Oxygen

Abstract

THIOL-BINDING agents such as N-ethylmaleimide¹, iodoacetamide² and hydroxymercuribenzoate³ are effective bacterial radiosensitizers, particularly with the more radioresistant bacteria². Sensitization of bacteria by these compounds is believed to be a result of their common ability to bind sulphydryl groups within the bacterial cell which can function either as natural radioprotective agents by radical scavenging or as repair agents for DNA radicals formed by hydrogen abstraction^4–6. Alternatively, enzyme repair reactions may be inhibited by the presence of these sulphydryl poisons, a view recently emphasized by Alexander, Lett and Dean⁷. Another group of radiosensitizing compounds are the stable free radicals such as oxygen⁸, nitric oxide⁹, di-t-butyl nitroxide¹⁰, and copper ions¹¹. Still a third class of compounds known to radiosensitize bacteria are halogen containing substances such as chloral hydrate¹² or chloroform¹³ which presumably act by the formation of short-lived halogen radicals toxic to the bacterial cell (the halogen containing sulphydryl poison iodoacetamide may be in this category too) or by formation of long lived toxic radiolytic product. Most of these agents are found to be more effective in nitrogen than in oxygen radiation conditions. Halogenated pyrimidines such as 5-bromouracil sensitize by yet another mechanism, because they require incorporation into cellular DNA in order to be effective.