Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada.
Aquat Toxicol. 2011 Oct;105(3-4):518-27. doi: 10.1016/j.aquatox.2011.08.005. Epub 2011 Aug 19.
Interactions of Cu, Cd and Zn were studied at the subcellular level in juvenile rainbow trout (Oncorhynchus mykiss) fed diets containing (μg/g) 500 Cu, 1000 Zn and 500 Cd singly and as a ternary mixture for 28 days. Livers were harvested and submitted to differential centrifugation to isolate components of metabolically active metal pool (MAP: heat-denaturable proteins (HDP), organelles, nuclei) and metabolically detoxified metal pool (MDP: heat stable proteins (HSP), NaOH-resistant granules). Results indicated that Cd accumulation was enhanced in all the subcellular compartments, albeit at different time points, in fish exposed to the metals mixture relative to those exposed to Cd alone, whereas Cu alone exposure increased Cd partitioning. Exposure to the metals mixture reduced (HDP) and enhanced (HSP, nuclei and granules) Cu accumulation while exposure to Zn alone enhanced Cu concentration in all the fractions analyzed without altering proportional distribution in MAP and MDP. Although subcellular Zn accumulation was less pronounced than that of either Cu or Cd, concentrations of Zn were enhanced in HDP, nuclei and granules from fish exposed to the metals mixture relative to those exposed to Zn alone. Cadmium alone exposure mobilized Zn and Cu from the nuclei and increased Zn accumulation in organelles and Cu in granules, while Cu alone exposure stimulated Zn accumulation in HSP, HDP and organelles. Interestingly, Cd alone exposure increased the partitioning of the three metals in MDP indicative of enhanced detoxification. Generally the accumulated metals were predominantly metabolically active: Cd, 67-83%; Cu, 68-79% and Zn, 60-76%. Taken together these results show both competitive and cooperative interactions dependent on the subcellular fraction, metal, exposure duration and relative metal exposure concentrations. Competitive interactions likely result from ionic mimicry with the metals displacing each other from common binding sites, whereas cooperative interactions suggest increased abundance of metal binding sites and/or existence of metal-specific non-interacting binding sites in some of the fractions. Moreover, the changes in subcellular distribution of the biometals Cu and Zn due to Cd exposure together with the shifts of the metals between MAP and MDP observed may have toxicological consequences.
在含有（μg/g）500Cu、1000Zn 和 500Cd 的饲料中，分别单独和作为三元混合物喂养 28 天后，研究了亚细胞水平上 Cu、Cd 和 Zn 的相互作用。从幼虹鳟（Oncorhynchus mykiss）肝脏中收获并进行差速离心，以分离代谢活跃的金属池（MAP：热变性蛋白（HDP）、细胞器、核）和代谢解毒的金属池（MDP：热稳定蛋白（HSP）、NaOH 抗性颗粒）的成分。结果表明，与单独暴露于 Cd 的鱼类相比，暴露于金属混合物中的鱼类所有亚细胞区室中的 Cd 积累均增加，尽管在不同时间点有所不同，而单独暴露于 Cu 会增加 Cd 的分配。暴露于金属混合物会降低（HDP）并增加（HSP、核和颗粒）Cu 积累，而单独暴露于 Zn 会增加所有分析部分的 Cu 浓度，而不会改变 MAP 和 MDP 中的比例分布。尽管亚细胞 Zn 积累不如 Cu 或 Cd 明显，但暴露于金属混合物中的鱼类的 HDP、核和颗粒中的 Zn 浓度增加，而单独暴露于 Zn 会增加 HSP、HDP 和细胞器中的 Zn 浓度。有趣的是，单独暴露于 Cd 会将 Zn 和 Cu 从核中动员出来，并增加细胞器中的 Zn 积累和颗粒中的 Cu 积累，而单独暴露于 Cu 会刺激 HSP、HDP 和细胞器中的 Zn 积累。有趣的是，单独暴露于 Cd 会增加 MDP 中三种金属的分配，表明解毒作用增强。通常，积累的金属主要是代谢活跃的：Cd，67-83%；Cu，68-79%和 Zn，60-76%。总的来说，这些结果表明，亚细胞区室、金属、暴露时间和相对金属暴露浓度的依赖性存在竞争和合作相互作用。竞争相互作用可能是由于离子模拟，金属从共同结合位点取代彼此，而合作相互作用表明一些部分中金属结合位点的丰度增加和/或存在特定于金属的非相互作用结合位点。此外，由于 Cd 暴露导致生物金属 Cu 和 Zn 的亚细胞分布发生变化，以及观察到的 MAP 和 MDP 之间金属的转移，可能会产生毒理学后果。
