Relative Effectiveness of Dithiol and Dithiocarbamate Chelating Agents in Reducing Retention of Polonium-210 in Rats

Abstract

Nine different sulphur-based chelators, including dithiols and dithiocarbamates, were examined for their ability to remove Po-210 from the rat. In general, treatments merely caused a redistribution of Po-210 in the body. Greatest reduction of Po-210 in blood was achieved by 2,3-dimercaptopropanol (BAL), sodium diethyldithiocarbamate (DDTC), and N-(2,3-dimercaptopropyl) phthalamidic acid (DMPA). Nearly all the compounds tested decreased Po-210 in the spleen and muscle. On the other hand, BAL and DDTC substantially increased the accumulation of Po-210 in the brain while DMPA, DMPS (sodium 2,3-dimercaptopropane-1-sulphonate) and DMSA (meso-2,3-dimercaptosuccinic acid) increased by several times the Po-210 in kidneys. A less pronounced increase of Po-210 was sometimes observed in liver (due to DDTC and DMPA) and in muscle (due to BAL and DDTC). Three of the dithiocarbamates (BGDTC, MeOBGDTC and BLDTC) did not increase accumulation of Po-210 in the brain and muscle but they reduced Po-210 in blood to a lesser degree than DDTC. A derivative of DMSA (Mi-ADMS) reduced Po-210 in blood, bone and muscle more than DMSA, but at the same time increased Po-210 in the kidney. When BAL or DDTC were combined with other agents there was a greater reduction in the whole-body burden of Po-210. Removal of Po-210 from the bone, spleen and kidneys by BAL was increased by repeated treatment. However, under similar experimental conditions the effect of a single injection of BAL on Po-210 in blood was less pronounced when the period of observation was prolonged. Total-body retention of Po-210 could not be reduced to less than 85% of the untreated controls by any of the chelators tested. In spite of this some of them (BAL, DMPS, DMSA, DMPA) could still have a useful role in reducing the toxicity of Po-210.

In vitro evaluation of the toxicity of several dithiocarbamates using anEscherichia coli growth inhibition bioassay and the acetylcholinesterase inhibition test

“…Yet because DTCs also have numerous pharmacological and sanitary applications ŽTopping and Jones, 1988;Andersen et al, 1989a, b;Basinger et al, 1989;Topping et al, 1989;Shelkova et al, 1990;Tanaka, 1990;Lee et al, 1991;Gale et al, 1992;Jones et al, 1992;Kojima et al, 1992; . Rencova et al, 1993;Hidaka et al, 1995 , the syn thesis of new DTCs is still underway. This means that continued, thorough research of their toxicological aspects is needed, including the application of fast and simple biological screening tests, in order to identify and control the production of those compounds that present or release high levels of toxicity.…”