Protective role of zinc-metallothionein on DNA damage in vitro by ferric nitrilotriacetate (Fe–NTA) and ferric salts

Abstract

Oxidative DNA damage can be caused by radicals generated by transitional metals like iron in Fenton reaction. Metallothionein (MT) may play an important role in preventing oxidative DNA damage. Therefore, after comparing the effects of ferric salts (Fe), and complexes of ferric salts with nitrilotriacetic acid (Fe–NTA) on DNA damage, the protective effects of zinc-MT (Zn-MT) on DNA damage of Fe salts or Fe–NTA were investigated in vitro. DNA damage was measured by loss of fluorescence of DNA binding to ethidium bromide, and also by increased DNA mobility in agarose gel electrophoresis. Both Fe salts and Fe–NTA could induce calf thymus DNA damage in presence of hydrogen peroxide and ascorbate. However, the degree of DNA damage was lower with Fe salts than that with Fe–NTA complex. Addition of 50 μM Zn-MT could only protect DNA from Fe–NTA, but not from Fe salt induced damage. The protective effect of MT was about five times better than that of glutathione (GSH). These results suggest a potential role for MT in protection from Fe–NTA-induced DNA damage.