Vettori M V, Gatti R, Orlandini G, Belletti S, Alinovi R, Smargiassi A, Mutti A
Department of Clinical Medicine, Nephrology & Health Sciences, Institutes of HistologyGeneral Pathology, University of Parma Medical School, Italy.
Toxicol In Vitro. 1999 Dec;13(6):931-8. doi: 10.1016/s0887-2333(99)00073-9.
PC12 (undifferentiated and differentiated) and C6 cells have been used to investigate kinetics, morphological and functional endpoints following exposure to MnCl(2) and manganic transferrin (Mn-Tf). Mn in undifferentiated (non-differentiated cells) exposed to both free (MnCl(2)) and bound Mn (Mn-Tf), was three- to fivefold lower as compared to differentiated (differentiated) PC12 cells and higher by one order of magnitude as compared to glial C6 cells. Exposure to both MnCl(2) and Mn-Tf was followed by time- and dose-dependent morphological changes characteristic of apoptosis, which was never observed in Mn-exposed C6 glial cells. Results from cell viability assays were consistent with apoptotic response rates quantified by cell count. Threshold concentrations for undifferentiated and differentiated PC12 cells were 10(-6) and 10(-5)m, respectively. Thus, despite their greater ability to accumulate Mn, differentiated PC12 cells are less sensitive to Mn-induced apoptosis. This model might be relevant to neuronal degeneration induced by Mn occurring in the developing brain and possibly in clinical manganism. Such critical doses at the cellular level seem to be consistent with Mn levels (5x10(-6)m) recorded in the basal ganglia of monkeys chronically exposed to Mn and developing clinical signs of manganism.
PC12细胞（未分化和分化的）和C6细胞已被用于研究暴露于氯化锰（MnCl₂）和锰转铁蛋白（Mn-Tf）后的动力学、形态学和功能终点。与分化的PC12细胞相比，未分化的（非分化细胞）暴露于游离锰（MnCl₂）和结合锰（Mn-Tf）时的细胞内锰（[Mn]i）低三到五倍，而与神经胶质C6细胞相比则高一个数量级。暴露于MnCl₂和Mn-Tf后，细胞出现了具有凋亡特征的时间和剂量依赖性形态变化，而在暴露于锰的C6神经胶质细胞中从未观察到这种变化。细胞活力测定结果与通过细胞计数量化的凋亡反应率一致。未分化和分化的PC12细胞的阈值浓度分别为10⁻⁶和10⁻⁵m。因此，尽管分化的PC12细胞积累锰的能力更强，但它们对锰诱导的凋亡不太敏感。该模型可能与发育中的大脑以及可能临床锰中毒中发生的锰诱导的神经元变性有关。细胞水平的这种临界剂量似乎与长期暴露于锰并出现临床锰中毒体征的猴子基底神经节中记录的锰水平（5×10⁻⁶m）一致。
