Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention.

Following accidental inhalation of radioactive cobalt particles, the poorly soluble and highly radioactive CoO particles are retained for long periods in lungs. To decrease their retention time is of crucial importance to minimize radiation-induced damage. As dissolved cobalt is quickly transferred to blood and eliminated by urinary excretion, enhancing the dissolution of particles would favor Co elimination. We evaluated the ability of ascorbic acid alone or associated with the chelating agents DTPA, DFOB or EDTA to enhance dissolution of cobalt particles after macrophage engulfment, and the drug effects on the translocation of the soluble species CoCl through an epithelial barrier. We exposed differentiated THP-1 macrophage-like cells and Calu-3 lung epithelial cells cultured in a bicameral system to cobalt and selected molecules up to 7 days. DTPA, the recommended treatment in man, used alone showed no effect, whereas ascorbic acid significantly increased dissolution of CoO particles. An additional efficacy in intracellular particles dissolution was observed for combinations of ascorbic acid with DTPA and EDTA. Except for DFOB, treatments did not significantly modify translocation of dissolved cobalt across the epithelial lung barrier. Our study provides new insights for decorporating strategies following radioactive cobalt particle intake.