Cadmium/zinc-metallothionein induces DNA strand breaks in vitro.
The in vitro DNA strand breaking activity of metallothionein (MT) containing Cd2+ and Zn2+ in a molar ratio of 5:2 is described. Studies with radical scavengers and electron paramagnetic resonance spectroscopy indicate that the DNA damage might be caused by a radical species formed by the native protein (i.e., MT) charged with the heavy metal ions. No DNA strand breaks are detectable with the heat-denatured MT or with Cd2+ or Zn2+ alone. Inhibition studies using EDTA as a metal ion chelator or N-ethylmaleimide to alkylate sulfhydryl groups suggest that both the bound heavy metal ions as well as the SH groups of the various cysteine residues of MT may be involved in the MT-dependent DNA cleavage. Further characterization showed that the DNA cleavage is more likely random than sequence- or base-specific. These observations may provide a clue in the search for initial events in Cd-related carcinogenicity.
Müller
T
T
INBIFO Institut für biologische Forschung, Köln, Federal Republic of Germany.
Schuckelt
R
R
Jaenicke
L
L
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D004587:Electrophoresis, Agar Gel; D016166:Free Radical Scavengers; D006863:Hydrogen-Ion Concentration; D008668:Metallothionein / Q000633:toxicity*; D051381:Rats; D013696:Temperature; D015032:Zinc / Q000633:toxicity*
D016166:Free Radical Scavengers; C004203:cadmium-binding protein; C021267:zinc thionein; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc