Several
thiol-containing molecules (TCM) are currently used as antidotes for
nickel, and vicinal TCM seem to be more effective in mobilizing tissue
nickel than are mono TCM. Using single cell alkaline electrophoresis, we have shown that the vicinal TCM, meso-2, 3-dimercaptosuccinic
acid (
DMSA), 2,3-dimercaptopropane-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 breaks 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 H(2)O(2) in
solution. H(2)O(2) alone did not, but H(2)O(2) plus Ni induced plasmid DNA breaks. Although Ni plus
glutathione did not break DNA, Ni plus
glutathione plus H(2)O(2) did. The Ni-
DMSA-induced DNA breaks in NB4 cells, as well as in plasmids, 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 H(2)O(2) produced by the vicinal TCM. The results that
DMSA at a concentration as low as 5 microM enhanced the Ni-induced DNA breaks suggest a further evaluation of the TCM as
nickel chelators is needed.