Selenoamino Acids as Radiation Protectors in Vitro

Abstract

The role of sulfhydryl compounds in reducing radiation damage to biological systems has been extensively studied. These compounds are known to react by mechanisms including free radical scavenger, repair of damage sites, and capacity to form mixed disulfides (1-3). We determined the specific influence of sulfhydryl compounds in reducing radiation damage to amino acids of cytochrome c, hemoglobin, and ovalbumin in solutions under anaerobic conditions (1). Results show that the sulfhydryl compounds offer considerable protection to the radiolabile amino acids such as histidine, methionine, phenylalanine, and cystine. Electron paramagnetic resonance studies on solid amino acids, peptides, and proteins indicate that radiation-induced unpaired electrons finally localize on sulfur atoms (4-8). Gordy and Miyagawa (4) suggested that unpaired electrons can migrate through certain segments of polypeptide chains of protein. Furthermore, Henriksen et al. (7, 8) showed an intermolecular transfer of unpaired electrons from protein molecules to sulfur protectors. Collectively, this evidence suggests that the ideal radiation protector is a molecule that can release and accept electrons and hydrogen atoms easily without itself becoming dissociated. If this is the case, selenoamino acids would be a better protector than analogous sulfur amino acids. This is because the ionization potential and bond energy of selenium compounds are smaller than that of sulfur compounds (9), and also selenium has more metallic character than sulfur (10). The biological function of selenium as a trace nutrient can be ascribed to the oxidation-reduction properties of compounds like selenoamino acids and selenoproteins (11, 12). Lipid antioxidant properties of selenoamino acids and selenoproteins have been described (11-14). Other mechanisms, especially free radical scavengers and repair of damage sites, are probably of great importance in its biological function. Selenium analogs of 2-aminoethylisothiouronium. HBr (AET) and related compounds have been synthesized, and the selenium analog of cysteamine has been shown to have a radiation-protective effect in mice (15). The purpose of this research is to test the effects and mechanisms of selenoamino