Fischer A B
Institute of Hygiene, Justus-Leibig-University, Giessen, Germany.
Analyst. 1995 Mar;120(3):975-8. doi: 10.1039/an9952000975.
An experimental system is presented for the assessment of the efficacy of chelating agents against cadmium. Mammalian cells in vitro can be employed to screen compounds that modify metal uptake, metal toxicity and metal mobilization from metal-loaded cells and can thus identify likely, or exclude unsuitable, candidates for the therapy or prevention of metal intoxification. Examples are given of possible cadmium antidotes. As a first step the toxicity of the chelating agents for different cells lines did not show appreciable differences. For the testing of the chelating agents a highly Cd-sensitive cell line was selected, which also exhibited a well measurable Cd uptake. The influence of the chelators on cadmium incorporation was studied and correlated with the results of experiments where the metal and the antidotes were simultaneously applied. Chelating agents causing reduced Cd uptake generally also depressed Cd toxicity. However, two or the compounds which led to increased cellular Cd incorporation did not modify metal cytotoxicity in a corresponding fashion. These paradoxical findings indicate complex interactions between chelators, metals and cells. Finally, cells were pre-treated with Cd and exposed to chelating agents. Only one of the substances tested, i.e., diethyldithiocarbamate, was capable of affecting Cd release from the cells. The results obtained with this model system show good agreement with finding reported in vivo.
本文介绍了一种用于评估螯合剂对镉疗效的实验系统。体外培养的哺乳动物细胞可用于筛选能够改变金属摄取、金属毒性以及从负载金属的细胞中动员金属的化合物，从而确定治疗或预防金属中毒的潜在候选药物，或排除不合适的候选药物。文中给出了可能的镉解毒剂的示例。第一步，螯合剂对不同细胞系的毒性未显示出明显差异。为了测试螯合剂，选择了一种对镉高度敏感的细胞系，该细胞系也表现出可测量的镉摄取。研究了螯合剂对镉掺入的影响，并将其与同时应用金属和解毒剂的实验结果相关联。导致镉摄取减少的螯合剂通常也会降低镉的毒性。然而，有两种化合物导致细胞内镉掺入增加，但并未相应地改变金属细胞毒性。这些矛盾的发现表明螯合剂、金属和细胞之间存在复杂的相互作用。最后，细胞先用镉预处理，然后暴露于螯合剂。所测试的物质中只有一种，即二乙基二硫代氨基甲酸盐，能够影响镉从细胞中的释放。用该模型系统获得的结果与体内报道的发现高度一致。
