O'Doherty Charles, Keenan Joanne, Horgan Karina, Murphy Richard, O'Sullivan Finbarr, Clynes Martin
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, D09 W6Y4, Ireland.
Alltech, Dunboyne, Meath, Ireland.
In Vitro Cell Dev Biol Anim. 2019 Apr;55(4):221-225. doi: 10.1007/s11626-019-00333-8. Epub 2019 Feb 23.
Copper is an essential dietary micronutrient in humans for proper cell function; however, in excess, it is toxic. The human cell line Caco-2 is popular as an in vitro model for intestinal absorption and toxicology. This study investigated the response of exponentially growing Caco-2 cells to prolonged copper exposure (120 h). An unexpected non-monotonic dose-response profile was observed in Caco-2 cells. Exposure to media supplemented with 3.125 μM CuSO resulted in decreased cell yield vs. untreated. However, toxicity was progressively reduced from 90% at 3.125 μM to 60% at 25 μM. This effect was documented between 48 and 120 h continuous exposure (p < 0.05). This triphasic toxicity curve was observed to be specific to copper in Caco-2 cells, as iron, manganese and zinc displayed monotonic dose-response profiles. Two inorganic copper forms, copper sulphate and copper chloride, were shown to conserve the non-monotonic dose-response curve. The triphasic effect was shown to be specific to Caco-2 cells. These results have implications for research investigating the effect of copper and other micronutrients using Caco-2 cells.
铜是人体必需的膳食微量营养素，对细胞正常功能至关重要；然而，过量的铜具有毒性。人细胞系Caco-2作为肠道吸收和毒理学的体外模型广受欢迎。本研究调查了指数生长的Caco-2细胞对长时间铜暴露（120小时）的反应。在Caco-2细胞中观察到了意外的非单调剂量反应曲线。与未处理的细胞相比，暴露于添加3.125μM硫酸铜的培养基中导致细胞产量下降。然而，毒性从3.125μM时的90%逐渐降低到25μM时的60%。在连续暴露48至120小时之间记录到了这种效应（p < 0.05）。观察到这种三相毒性曲线是Caco-2细胞中铜所特有的，因为铁、锰和锌呈现单调剂量反应曲线。两种无机铜形式，硫酸铜和氯化铜，都呈现出非单调剂量反应曲线。已证明这种三相效应是Caco-2细胞所特有的。这些结果对使用Caco-2细胞研究铜和其他微量营养素作用的研究具有启示意义。
