Müller T, Schuckelt R, Jaenicke L
INBIFO Institut für biologische Forschung, Köln, Federal Republic of Germany.
Arch Toxicol. 1991;65(1):20-6. doi: 10.1007/BF01973498.
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.
描述了镉离子（Cd2+）与锌离子（Zn2+）摩尔比为5:2的金属硫蛋白（MT）的体外DNA链断裂活性。使用自由基清除剂和电子顺磁共振光谱进行的研究表明，DNA损伤可能是由结合了重金属离子的天然蛋白质（即MT）形成的自由基物种引起的。热变性的MT或单独的Cd2+或Zn2+均未检测到DNA链断裂。使用乙二胺四乙酸（EDTA）作为金属离子螯合剂或N-乙基马来酰亚胺使巯基烷基化的抑制研究表明，结合的重金属离子以及MT各个半胱氨酸残基的巯基可能都参与了MT依赖性的DNA切割。进一步的表征表明，DNA切割更可能是随机的，而不是序列特异性或碱基特异性的。这些观察结果可能为寻找镉相关致癌作用的初始事件提供线索。
