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4 April 2012 Utilization of the Ferrous Sulfate (Fricke) Dosimeter for Evaluating the Radioprotective Potential of Cystamine: Experiment and Monte Carlo Simulation
Ridthee Meesat, Sunuchakan Sanguanmith, Jintana Meesungnoen, Martin Lepage, Abdelouahed Khalil, Jean-Paul Jay-Gerin
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Abstract

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.

Ridthee Meesat, Sunuchakan Sanguanmith, Jintana Meesungnoen, Martin Lepage, Abdelouahed Khalil, and Jean-Paul Jay-Gerin "Utilization of the Ferrous Sulfate (Fricke) Dosimeter for Evaluating the Radioprotective Potential of Cystamine: Experiment and Monte Carlo Simulation," Radiation Research 177(6), 813-826, (4 April 2012). https://doi.org/10.1667/RR2829.1
Received: 12 October 2011; Accepted: 1 December 2011; Published: 4 April 2012
JOURNAL ARTICLE
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