The Protection of Mice against Radiation by 2-Mercaptoethylguanidine and Its Disulfide

Abstract

Some sulfhydryl compounds lose their ability to protect against ionizing radiation when they are administered in the oxidized state. Oxidized glutathione (1, 2) and cystine (3), the oxidized form of cysteine, are inactive as protectors, whereas cystamine (4-7), the oxidized form of cysteamine, is highly effective in reducing the injurious effects of radiation. Gordy and Miyagawa (8) have suggested that cystamine is effective only on its reduction to cysteamine within the animal cell. 2-Mercaptoethylguanidine (MEG) is formed by transguanylation when S-(2aminoethyl)thiuronium bromide hydrobromide (AET) is dissolved in aqueous buffered solutions at neutral pH (9). Hence, MEG rather than AET has usually been the substance administered in previously reported protective studies. MEG is readily oxidized in mildly alkaline solutions to bis(2-guanidoethyl) disulfide (GED), and solutions of MEG are therefore frequently contaminated with the disulfide. In their survey of related compounds with protective activity, Shapira et al. (10) observed that GED, as well as MEG, protected mice against radiation. The present study was undertaken to investigate, in greater detail, the relationship between the state of oxidation of this agent prior to administration, and its therapeutic efficiency.