Zödl Bettina, Zeiner Michaela, Marktl Wolfgang, Steffan Ilse, Ekmekcioglu Cem
Department of Physiology, Faculty of Medicine, University of Vienna, A-1090 Vienna, Austria.
Biol Trace Elem Res. 2003 Winter;96(1-3):143-52. doi: 10.1385/BTER:96:1-3:143.
Copper might be toxic to human intestinal cells because of its ability to catalyze the formation of free radicals. The aim of the present study was to quantify toxicological effects of increasing copper concentrations in preconfluent, colonic cancerous cells as well as in postconfluent, differentiating Caco-2 cells. Our results indicate that postconfluent cells might be more sensitive to copper toxicity. A significant rise of lactate dehydrogenase (LDH) release (150 microM or above) and decrease of cell proliferation (100 microM or above) with increasing copper levels was found, as compared to the control. To the contrary, preconfluent cells were not significantly affected by copper (LDH release) or, if so, only at a concentration of 250 microM (proliferation). Loss of viability and morphological changes, including loss of adherence and cell rounding, were visible after incubation with 250 microM copper in both groups. Superoxide dismutase (SOD) activities were not affected by copper. Glutathione peroxidase (GSH-Px) and catalase activities were higher in copper-treated cells, especially in the postconfluent ones (nevertheless, the results were not significant because of high standard deviations). In conclusion, we demonstrated that copper exerts intracellular, toxicological effects on both groups of Caco-2 cells, although the effects seem to be more evident in the postconfluent (enterocytelike) group. Risk assessment, especially for high concentrations, might be of special interest.
铜可能因其催化自由基形成的能力而对人体肠道细胞有毒性。本研究的目的是量化预汇合的结肠癌细胞以及汇合后正在分化的Caco-2细胞中铜浓度增加所产生的毒理学效应。我们的结果表明，汇合后细胞可能对铜毒性更敏感。与对照组相比，随着铜水平的增加，乳酸脱氢酶（LDH）释放显著增加（150 microM及以上），细胞增殖显著降低（100 microM及以上）。相反，预汇合细胞未受到铜的显著影响（LDH释放），或者即便受到影响，也仅在250 microM浓度时（细胞增殖）。两组细胞在与250 microM铜孵育后均出现活力丧失和形态变化，包括贴壁丧失和细胞变圆。超氧化物歧化酶（SOD）活性不受铜的影响。谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶活性在铜处理的细胞中较高，尤其是在汇合后的细胞中（然而，由于标准差较高，结果不显著）。总之，我们证明了铜对两组Caco-2细胞均产生细胞内毒理学效应，尽管这种效应在汇合后（类似肠细胞）组中似乎更明显。风险评估，尤其是对高浓度的风险评估，可能具有特殊意义。
