Evidence that the reactions of cadmium in the presence of metallothionein can produce hydroxyl radicals

A variety of Cu reconstituted metallothioneins (MTs) containing different a mounts 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, H<INF>2</INF>O< INF>2</INF> enhanced DMPO/.OH adduct formation, catalase and the Cu (I) spe cific chelating agent bathocuproine, reduced DMPO/.OH adduct formation. The se results suggest that Cu (I) and H<INF>2</INF>O<INF>2</INF> both have imp ortant roles in the production of active species in these<INF></INF> system s and cause DMPO/.OH formation. However, Cd<INF>7</INF>-MT showed no abilit y to cause generation of DMPO adducts with H<INF>2</INF>O<INF>2</INF> seemi ng to indicate cadmium is not a Fenton metal. To test this hypothesis furth er trapping studies were run with added sulphite and lipid peroxide using b oth commercial MT and Cd<INF>7</INF>-MT since cadmium causes peroxidation i n vivo. Commercial MT generates radicals with added sulphite and peroxide, Cd<INF>7</INF>-MT does not, demonstrating that cadmium is not a Fenton meta l. These results help to explain the oxidative damage to DNA observed in th e presence of MT and cadmium in vitro.