Evidence that the reactions of cadmium in the presence of metallothionein can produce hydroxyl radicals.
A variety of Cu reconstituted metallothioneins (MTs) containing different amounts of copper ions together with Cd7-MT free of copper were prepared and used in spin trapping experiments designed to show cadmium is not a Fenton active metal. A significant increase of the DMPO/.OH adduct was observed, with increased concentrations of the copper containing MTs, H2O2 enhanced DMPO/.OH adduct formation, catalase and the Cu (I) specific chelating agent bathocuproine, reduced DMPO/.OH adduct formation. These results suggest that Cu (I) and H2O2 both have important roles in the production of active species in these systems and cause DMPO/.OH formation. However, Cd7-MT showed no ability to cause generation of DMPO adducts with H2O2 seeming to indicate cadmium is not a Fenton metal. To test this hypothesis further trapping studies were run with added sulphite and lipid peroxide using both commercial MT and Cd7-MT since cadmium causes peroxidation in vivo. Commercial MT generates radicals with added sulphite and peroxide, Cd7-MT does not, demonstrating that cadmium is not a Fenton metal. These results help to explain the oxidative damage to DNA observed in the presence of MT and cadmium in vitro.
O'Brien
P
P
Department of Chemistry, Imperial College of Science, Technology and Medicine, University of London, UK.
Salacinski
H J
HJ
D002104:Cadmium / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy; D017665:Hydroxyl Radical / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008668:Metallothionein / Q000494:pharmacology*; D015203:Reproducibility of Results
D003497:Cyclic N-Oxides; D002104:Cadmium; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D003300:Copper; D008668:Metallothionein