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 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.
Lynn
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Institute of Zoology, Academia Sinica, Taipei, Taiwan, 11529, Republic of China.
Yu
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GL
Yan
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K
D002460:Cell Line / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004112:Dimercaprol / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008623:Mercaptoethanol / Q000494:pharmacology; D009532:Nickel / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D010084:Oxidation-Reduction; D010398:Penicillic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010957:Plasmids / Q000187:drug effects; D004113:Succimer / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D004112:Dimercaprol; C028100:penicillamide; D008623:Mercaptoethanol; C022838:nickel chloride; D009532:Nickel; D004050:Ditiocarb; D004113:Succimer; D005978:Glutathione; D010398:Penicillic Acid