Cystamine, an organic disulfide (RSSR), is among the best of the known radiation-protective compounds and has been used to protect normal tissues in clinical radiation therapy. Recently, it has also proved to be beneficial in the treatment of disorders of the central nervous system in animal models. However, the underlying mechanism of its action at the chemical level is not yet well understood. The present study aims at using the ferrous sulfate (Fricke) dosimeter to quantitatively evaluate, both experimentally and theoretically, the radioprotective potential of this compound. The well-known radiolysis of the Fricke dosimeter by 60Co γ rays or fast electrons, based on the oxidation of ferrous ions to ferric ions by the oxidizing species •OH, HO2•, and H2O2 produced in the radiolytic decomposition of water, forms the basis for our method. The presence of cystamine in Fricke dosimeter solutions during irradiation prevents the radiolytic oxidation of Fe2 and leads to decreased ferric yields (or G values). The observed decrease in G(Fe3 ) increases upon increasing the concentration of the disulfide compound over the range 0–0.1 M under both aerated and deaerated conditions. To help assess the basic radiation-protective mechanism of this compound, a full Monte Carlo computer code is developed to simulate in complete detail the radiation-induced chemistry of the studied Fricke/cystamine solutions. Benefiting from the fact that cystamine is reasonably well characterized in terms of radiation chemistry, this computer model proposes reaction mechanisms and incorporates specific reactions describing the radiolysis of cystamine in aerated and deaerated Fricke solutions that lead to the observable quantitative chemical yields. Results clearly indicate that the protective effect of cystamine originates from its radical-capturing ability, which allows this compound to act by competing with the ferrous ions for the various free radicals – especially •OH radicals and H• atoms – formed during irradiation of the surrounding water. Most interestingly, our simulation modeling also shows that the predominant pathway in the oxidation of cystamine by •OH radicals involves an electron-transfer mechanism, yielding RSSR• and OH–. A very good agreement is found between calculated G(Fe3 ) values and experiment. This study concludes that Monte Carlo simulations represent a very efficient method for understanding indirect radiation damage at the molecular level.
You have requested a machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Neither BioOne nor the owners and publishers of the content make, and they explicitly disclaim, any express or implied representations or warranties of any kind, including, without limitation, representations and warranties as to the functionality of the translation feature or the accuracy or completeness of the translations.
Translations are not retained in our system. Your use of this feature and the translations is subject to all use restrictions contained in the Terms and Conditions of Use of the BioOne website.
Vol. 177 • No. 6