Vicinal-thiol-containing molecules enhance but mono-thiol-containing molecules reduce nickel-induced DNA strand breaks

Several thiol-containing molecules (TCM) are currently used as antidotes fo r nickel, and vicinal TCM seem to be more effective in mobilizing tissue ni ckel than are mono TCM. Using single cell alkaline electrophoresis, we have shown that the vicinal TCM, meso-2,3-dimercaptosuccinic acid (DMSA), 2,3-d imercaptopropane-1-sulfonate, and 2,3-dimercaptopropanol markedly enhanced, whereas the mono TCM, D-penicillamide, glutathione, beta-mercaptoethanol, and diethyl dithiocarbomate, reduced nickel chloride (Ni)-induced DNA break s in a human leukemia cell line, NB4 cells. Ni or TCM alone did not induce plasmid DNA breaks in test tubes and neither did Ni plus mono TCM; however, Ni plus vicinal TCM did. Vicinal TCM did, but mono TCM did not generate H2 O2, in solution. H2O2 alone did hot, but H2O2 plus Ni induced plasmid DNA b reaks. Although Ni plus glutathione did not break DNA, Ni plus glutathione plus H2O2 did. The Ni-DMSA-induced DNA breaks in NB4 cells, as well as in p lasmids, were completely prevented by D-mannitol or partially prevented by several antioxidants. Therefore, the DNA breaks induced by Ni plus vicinal TCM seem to be due to the complex of Ni with TCM in concert with the H2O2 p roduced by the vicinal TCM. The results that DMSA at a concentration as low as 5 mu M enhanced the Ni-induced DNA breaks suggest a further evaluation of the TCM as nickel chelators is needed. (C) 1999 Academic Press.