Zödl Bettina, Zeiner Michaela, Sargazi Mansour, Roberts Norman B, Marktl Wolfgang, Steffan Ilse, Ekmekcioglu Cem
Department of Physiology, Faculty of Medicine, University of Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria.
J Inorg Biochem. 2003 Dec 1;97(4):324-30. doi: 10.1016/s0162-0134(03)00312-x.
Zinc (in relatively high concentrations) can be toxic to intestinal cells. The aim of the present study was to quanitfy cellular injury in preconfluent, colonic cancerous cells and in postconfluent, differentiating human intestinal Caco-2 cells. Cellular damage was measured by using cell proliferation, lactate dehydrogenase (LDH)-release, and apoptosis studies. Furthermore, the activities of the major antioxidative enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase] and differentiation markers (alkaline phosphatase and aminopeptidase-N) were determined after exposure of the cells to increasing amounts of zinc sulfate. Proliferation and viability decreased in a concentration-dependent manner. A noticeable increase of LDH-release correlated to cell rounding and detachment at relatively high zinc levels (200 muM) was observed in both groups of cells. Above 100 muM of zinc, significant apoptotic activity was found in the preconfluent cells. Zinc supplementation did not alter SOD activities. However, GPx and, in part, catalase activities tended to be higher in zinc-treated cells (nevertheless the results were not significant). Differentiation markers were noticeably induced by increasing amounts of zinc, especially in the preconfluent cells. In conclusion, we suggest that the susceptibility to zinc induced damage is equal in both confluentation groups of Caco-2 cells. Risk assessment for high concentrations seems recommendable.
锌（相对高浓度时）可能对肠道细胞有毒性。本研究的目的是量化融合前的结肠癌细胞和融合后正在分化的人肠Caco-2细胞中的细胞损伤。通过细胞增殖、乳酸脱氢酶（LDH）释放和凋亡研究来测量细胞损伤。此外，在细胞暴露于增加量的硫酸锌后，测定主要抗氧化酶[超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶]的活性以及分化标志物（碱性磷酸酶和氨肽酶-N）的活性。增殖和活力以浓度依赖性方式降低。在两组细胞中均观察到，在相对高的锌水平（200μM）下，LDH释放的显著增加与细胞变圆和脱离相关。在融合前的细胞中，锌浓度高于100μM时，发现有明显的凋亡活性。补充锌并未改变SOD的活性。然而，锌处理的细胞中GPx以及部分过氧化氢酶的活性倾向于更高（尽管结果不显著）。增加量的锌显著诱导分化标志物，尤其是在融合前的细胞中。总之，我们认为Caco-2细胞的两个融合组对锌诱导损伤的易感性相同。对于高浓度进行风险评估似乎是可取的。
