Cai L, Tsiapalis G, Cherian M G
Department of Pathology, University of Western Ontario, London, Canada.
Chem Biol Interact. 1998 Sep 4;115(2):141-51. doi: 10.1016/s0009-2797(98)00069-6.
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 microM 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.
氧化型DNA损伤可由芬顿反应中像铁这样的过渡金属产生的自由基引起。金属硫蛋白(MT)可能在预防氧化型DNA损伤中发挥重要作用。因此,在比较铁盐(Fe)以及铁盐与次氮基三乙酸的复合物(Fe-NTA)对DNA损伤的影响之后,体外研究了锌-金属硫蛋白(Zn-MT)对铁盐或Fe-NTA所致DNA损伤的保护作用。通过与溴化乙锭结合的DNA荧光丧失来测定DNA损伤,同时也通过琼脂糖凝胶电泳中DNA迁移率增加来测定。在过氧化氢和抗坏血酸存在的情况下,铁盐和Fe-NTA均可诱导小牛胸腺DNA损伤。然而,铁盐所致的DNA损伤程度低于Fe-NTA复合物。添加50微摩尔的Zn-MT仅能保护DNA免受Fe-NTA的损伤,而不能保护其免受铁盐诱导的损伤。MT的保护作用比谷胱甘肽(GSH)约强五倍。这些结果表明MT在预防Fe-NTA诱导的DNA损伤中具有潜在作用。