Kamunde Collins
Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada.
Aquat Toxicol. 2009 Mar 9;91(4):291-301. doi: 10.1016/j.aquatox.2008.10.013. Epub 2008 Oct 30.
Non-essential metals such as cadmium (Cd) accumulated in animal cells are envisaged to partition into potentially metal-sensitive compartments when detoxification capacity is exceeded. An understanding of intracellular metal partitioning is therefore important in delineation of the toxicologically relevant metal fraction for accurate tissue residue-based assessment of toxicity. In the present study, the early intracellular Cd accumulation was studied to test the prediction that it conforms to the spillover model of metal toxicity. Juvenile rainbow trout (10-15g) were exposed for 96h to three doses of cadmium (5, 25 and 50microg/l) and a control (nominal 0microg/l Cd) in hard water followed by measurement of the changes in intracellular Cd concentrations in the gill and liver, and carcass calcium (Ca) levels. There were dose-dependent increases in Cd concentration in both organs but the accumulation pattern over time was linear in the liver and biphasic in the gill. The Cd accumulation was associated with carcass Ca loss after 48h. Comparatively, the gill accumulated 2-4x more Cd than the liver and generally the subcellular compartments reflected the organ-level patterns of accumulation. For the gill the rank of Cd accumulation in subcellular fractions was: heat-stable proteins (HSP)>heat-labile proteins (HLP)>nuclei>microsomes-lysosomes (ML)>/=mitochondria>resistant fraction while for the liver it was HSP>HLP>ML>mitochondria>nuclei>resistant fraction. Contrary to the spillover hypothesis there was no exposure concentration or internal accumulation at which Cd was not found in potentially metal-sensitive compartments. The proportion of Cd bound to the metabolically active pool (MAP) increased while that bound to the metabolically detoxified pool (MDP) decreased in gills of Cd-exposed fish but remained unchanged in the liver. Because the Cd concentration increased in all subcellular compartments while their contribution to the total increased, decreased or remained unchanged following Cd exposure, use of percentage data to infer spillover requires caution.
当解毒能力被超过时,动物细胞中积累的非必需金属如镉(Cd)被设想会分配到潜在的金属敏感区室中。因此,了解细胞内金属分配对于确定毒理学相关的金属部分很重要,以便基于准确的组织残留来评估毒性。在本研究中,研究了早期细胞内镉的积累情况,以检验其是否符合金属毒性的溢出模型这一预测。将幼年虹鳟(10 - 15克)在硬水中暴露于三种镉剂量(5、25和50微克/升)以及一个对照(名义上0微克/升镉)96小时,随后测量鳃、肝脏中的细胞内镉浓度变化以及鱼体钙(Ca)水平。两个器官中的镉浓度均呈剂量依赖性增加,但随着时间的积累模式在肝脏中是线性的,在鳃中是双相的。48小时后,镉的积累与鱼体钙流失有关。相比之下,鳃积累的镉比肝脏多2 - 4倍,并且一般亚细胞区室反映了器官水平的积累模式。对于鳃,亚细胞组分中镉积累的顺序为:热稳定蛋白(HSP)>热不稳定蛋白(HLP)>细胞核>微粒体 - 溶酶体(ML)>=线粒体>抗性组分,而对于肝脏则是HSP>HLP>ML>线粒体>细胞核>抗性组分。与溢出假说相反,在任何暴露浓度或内部积累情况下,在潜在的金属敏感区室中都能发现镉。在暴露于镉的鱼的鳃中,与代谢活性池(MAP)结合的镉比例增加,而与代谢解毒池(MDP)结合的镉比例下降,但在肝脏中保持不变。由于所有亚细胞区室中的镉浓度都增加了,而它们对总量的贡献在镉暴露后增加、减少或保持不变,因此使用百分比数据推断溢出时需要谨慎。