Sliwinski Tomasz, Czechowska Agnieszka, Kolodziejczak Magdalena, Jajte Jolanta, Wisniewska-Jarosinska Maria, Blasiak Janusz
Department of Molecular Genetics, University of Lodz, Lodz, Poland.
Cell Biol Int. 2009 Apr;33(4):542-7. doi: 10.1016/j.cellbi.2009.02.004. Epub 2009 Feb 28.
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 (ZnSO(4)) in normal human lymphocytes and human myelogenous leukemia K562 cancer cells in the presence of zinc and hydrogen peroxide (H(2)O(2)). Zinc at concentrations from the range 10-1000 microM 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 H(2)O(2), since the element exerted a protective effect against cyto- and geno-toxic action of H(2)O(2) in the former, whereas it increased such action in the latter. Zinc inhibited the repair of DNA damage induced by H(2)O(2) 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.
锌在广泛的细胞过程中发挥着至关重要的作用，包括抵御自由基和维持基因组稳定性。锌在某些蛋白质中的存在对于它们作为转录因子发挥功能至关重要。关于锌与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道以及这些报道有时相互矛盾的性质，这一点可能很重要。在本研究中，我们研究了在锌和过氧化氢（H₂O₂）存在的情况下，硫酸锌（ZnSO₄）对正常人淋巴细胞和人髓性白血病K562癌细胞的细胞毒性和遗传毒性。浓度范围为10 - 1000微摩尔的锌降低了癌细胞的活力，而且这种作用，尤其是对于低浓度的该元素，在癌细胞中比在正常细胞中更为明显。锌在正常细胞中未诱导DNA损伤，但在癌细胞中却会诱导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，因为该元素对前者中H₂O₂的细胞毒性和遗传毒性作用具有保护作用，而在后者中却增强了这种作用。锌抑制了癌细胞中由H₂O₂诱导的DNA损伤的修复。结果表明，锌可能保护正常细胞免受DNA损伤作用，并增强癌细胞中的这种作用，这表明该元素根据靶细胞的不同具有双重作用，并且可能在癌症治疗中有用。
