Induction of oxidative DNA damage by carcinogenic metals
Induction of oxidative DNA damage by carcinogenic metals
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DOI：
10.1016/s0378-4274(01)00483-0
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发表时间：
2002-02-28
影响因子：
3.5
通讯作者：
Kasprzak, KS
中科院分区：
文献类型：
--
作者：
Bal, W;Kasprzak, KS
对人体有致癌作用的金属离子有As、Be、Cd、Cr和Ni，候选者还包括Co、Cu、Fe和Pt。提出了一系列的分子机制，这些金属，反映其不同的化学性质。金属致癌作用中的氧化概念提出，在体内形成的上述金属（Co、Cr、Cu、Fe、Ni）的某些络合物经历氧化还原循环，产生氧化DNA的活性氧物质和/或高价金属离子。氧化性DNA损伤的一些产物，包括8-氧代鸟嘌呤和链断裂，诱导突变，这可能导致肿瘤转化。在细胞核中的金属结合模式和它们的反应性的建立对于理解金属致癌的分子事件是至关重要的。我们提出了镍（II）和铜（II）在核心组蛋白（H3，H2 A）和精子鱼精蛋白（HP 2）的结合位点，并使用分子模型，提供证据的产生promutagenic氧化DNA损伤的结合金属。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
The metal ions carcinogenic to humans are As, Be, Cd, Cr and Ni, and the candidates also include Co, Cu, Fe and Pt. A range of molecular mechanisms was proposed for these metals, reflecting their diverse chemical properties. The oxidative concept in metal carcinogenesis proposes that some complexes of the above metals (Co, Cr, Cu, Fe, Ni) formed in vivo undergo redox cycling, yielding reactive oxygen species and/or high valence metal ions which oxidize DNA. Some of the products of oxidative DNA damage, including 8-oxoguanine and strand breaks, induce mutations, which may lead to neoplastic transformation. The establishment of metal-binding modes in the cell nucleus and of their reactivity is crucial for the understanding of molecular events in metal carcinogenesis. We have proposed the binding sites for Ni(II) and Cu(II) in core histones (H3, H2A) and sperm protamines (HP2) and, using molecular models, provided evidence for the generation of promutagenic oxidative DNA damage by the bound metals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.