Zinc salts differentially modulate DNA damage in normal and cancer cells
Zinc salts differentially modulate DNA damage in normal and cancer cells
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DOI：
10.1016/j.cellbi.2009.02.004
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发表时间：
2009-04-01
影响因子：
3.9
通讯作者：
Blasiak, Janusz
中科院分区：
文献类型：
--
作者：
Sliwinski, Tomasz;Czechowska, Agnieszka;Blasiak, Janusz
锌在多种细胞过程中发挥着重要作用，包括防御自由基和维持基因组稳定性。一些蛋白质中锌的存在对于它们作为转录因子的功能至关重要。关于锌和 DNA 之间的相互作用知之甚少，鉴于有关锌在癌症转化中的作用的报告以及这些报告有时相互矛盾的特征，这一点可能很重要。在本研究中，我们研究了硫酸锌 (ZnSO4) 在锌和过氧化氢 (H2O2) 存在下对正常人淋巴细胞和人骨髓性白血病 K562 癌细胞的细胞毒性和基因毒性。浓度在 10-1000 μM 范围内的锌会降低癌细胞的活力，这种效应，特别是对于低浓度的元素，比正常细胞更明显。锌不会在正常细胞中引起DNA损伤，但会在癌细胞中引起DNA损伤。我们观察到，在 H2O2 存在的情况下，锌在正常细胞和癌细胞中的作用存在关键差异，因为该元素在前者中对 H2O2 的细胞和基因毒性作用发挥了保护作用，而在后者中则增强了这种作用。锌抑制癌细胞中 H2O2 诱导的 DNA 损伤的修复。结果表明，锌可以保护正常细胞免受 DNA 损伤作用，并增强癌细胞中的这种作用，这表明该元素具有依赖靶细胞的双重作用，可用于癌症治疗。 (C) 2009 年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
Zinc plays an essential role in a wide range of cellular processes, including defense against free radicals and maintaining genomic stability. The presence of zinc in some proteins is fundamental for their functioning as transcription factors. Little is known about interaction between zinc and DNA, which can be important in light of reports on the role of zinc in cancer transformation and sometimes contradictory character of these reports. In the present study we studied cyto- and genotoxicity of zinc sulfate (ZnSO4) in normal human lymphocytes and human myelogenous lukemia K562 cancer cells in the presence of zinc and hydrogen peroxide (H2O2). Zinc at concentrations from the range 10-1000 mu M decreased the viability of cancer cells and this effect, especially for low concentrations of the element, was much more pronounced than in normal cells. Zinc did not induce DNA damage in normal cells, but did so in cancer cells. We observed a key difference between the action of zinc in normal and cancer cells in the presence of H2O2, since the element exerted a protective effect against cyto- and geno-toxic action of H2O2 in the former, whereas it increased such action in the latter. Zinc inhibited the repair of DNA damage induced by H2O2 in cancer cells. The results suggest that zinc may protect normal cells against DNA-damaging action and increase this action in cancer cells, which indicates the dual action of this element in dependency of target cells and can be useful in cancer therapy. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.