Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, 1240 N 10th St, Milwaukee, WI, USA.
School of Public Health, Guangxi Medical University, 22 Shuangyong Rd, Nanning, Guangxi, China.
Environ Sci Pollut Res Int. 2018 Jun;25(16):15378-15389. doi: 10.1007/s11356-018-1752-5. Epub 2018 Mar 21.
Manganese (Mn) is considered as an emerging metal contaminant in the environment. However, its potential interactions with companying toxic metals and the associated mixture effects are largely unknown. Here, we investigated the toxicity interactions between Mn and two commonly seen co-occurring toxic metals, Pb and Cd, in a model organism the nematode Caenorhabditis elegans. The acute lethal toxicity of mixtures of Mn+Pb and Mn+Cd were first assessed using a toxic unit model. Multiple toxicity endpoints including reproduction, lifespan, stress response, and neurotoxicity were then examined to evaluate the mixture effects at sublethal concentrations. Stress response was assessed using a daf-16::GFP transgenic strain that expresses GFP under the control of DAF-16 promotor. Neurotoxicity was assessed using a dat-1::GFP transgenic strain that expresses GFP in dopaminergic neurons. The mixture of Mn+Pb induced a more-than-additive (synergistic) lethal toxicity in the worm whereas the mixture of Mn+Cd induced a less-than-additive (antagonistic) toxicity. Mixture effects on sublethal toxicity showed more complex patterns and were dependent on the toxicity endpoints as well as the modes of toxic action of the metals. The mixture of Mn+Pb induced additive effects on both reproduction and lifespan, whereas the mixture of Mn+Cd induced additive effects on lifespan but not reproduction. Both mixtures seemed to induce additive effects on stress response and neurotoxicity, although a quantitative assessment was not possible due to the single concentrations used in mixture tests. Our findings demonstrate the complexity of metal interactions and the associated mixture effects. Assessment of metal mixture toxicity should take into consideration the unique property of individual metals, their potential toxicity mechanisms, and the toxicity endpoints examined.
锰（Mn）被认为是环境中一种新兴的金属污染物。然而，其与共存有毒金属的潜在相互作用以及相关的混合物效应在很大程度上尚不清楚。在这里，我们研究了模型生物秀丽隐杆线虫中 Mn 与两种常见共存有毒金属 Pb 和 Cd 之间的毒性相互作用。首先使用毒性单位模型评估了 Mn+Pb 和 Mn+Cd 混合物的急性致死毒性。然后，检查了多个毒性终点，包括繁殖、寿命、应激反应和神经毒性，以评估亚致死浓度下的混合物效应。应激反应通过表达 GFP 的 daf-16::GFP 转基因菌株进行评估，该 GFP 在 DAF-16 启动子的控制下表达。神经毒性通过表达 GFP 在多巴胺能神经元中的 dat-1::GFP 转基因菌株进行评估。Mn+Pb 混合物在蠕虫中诱导出超过加性（协同）致死毒性，而 Mn+Cd 混合物诱导出低于加性（拮抗）毒性。混合物对亚致死毒性的影响显示出更复杂的模式，并且取决于毒性终点以及金属的毒性作用模式。Mn+Pb 混合物对繁殖和寿命均产生加性效应，而 Mn+Cd 混合物对寿命但不对繁殖产生加性效应。两种混合物似乎对应激反应和神经毒性都产生加性效应，尽管由于混合物测试中使用的单一浓度，无法进行定量评估。我们的研究结果表明金属相互作用的复杂性及其相关的混合物效应。金属混合物毒性的评估应考虑到单个金属的独特性质、它们潜在的毒性机制以及所检查的毒性终点。
