稀土元素La、Gd和Ce对培养大鼠细胞生物学效应的研究

摘要

Objective　To investigate the biological effects and the effecting mechanisms of rare earth elements La，Gd and Ce on cultured rat cells.Methods　The biological effects of La3+ on cultured rat cells and the subcellular distribution of La and Gd and Ce, and the inflow of 45Ca2+ into the cells and total cellular calcium were measured by isotopic tracing, Proton Induced X Ray Emission Analysis (PIXE) and the techniques of biochemistry and cellular biology.Results　La3+ at the concentration of 10-10(or 10-9)～10-6mol/L significantly increased quantity of incorporation of 3H-TdR into DNA, total cellular protein and the activity of succinic dehydrogenase of mitochondria. The cell cycle analysis showed that the proportions of cells in S phase were accordingly increased acted by La3+ at above range of concentration. But these values were significantly decreased when concentration of La3+ raised to 10-4～10-3mol/L. It was further discovered that La，Gd，and Ce distributed mostly in the nuclei, and then in membranes. Gd and Ce also promoted the inflow of 45Ca2+ into the cells and increased the total calcium content in cells.Conclusions　① La3+ at a wide concentration range of 10-10( or 10-9)～10-6mol/L promotes proliferation of cultured rat cells, but at even higher concentration (10-4～10-3mol/L) shows cellular toxicity, and there is a striking dose-effect relationship. ② La，Gd and Ce can enter the cells and mainly distribute in the nuclei. ③ Gd and Ce can promote the inflow of extracellular Ca2+ into the cells and increase total cellular calcium.%目的在细胞水平上研究稀土元素（REE）La、Gd和Ce对培养大鼠细胞的生物学作用及机制。方法采用同位素示踪、质子激发X荧光分析（PIXE）结合生化及细胞学等技术观察La对细胞的生物学作用，La、Gd及Ce的亚细胞分布及Gd、Ce对细胞钙含量及钙内流的影响。结果 La3+在10-10(或10-9)～10-6mol/L时促进细胞蛋白质合成、线粒体琥珀酸脱氢酶活性增加、DNA合成以及S期细胞比率增加，但La3+在高剂量时（10-4～10-3mol/L）降低平滑肌细胞总蛋白质含量、抑制线粒体琥珀酸脱氢酶活性以及S期细胞比率减少。通过PIXE发现La、Gd、Ce可进入细胞，且在核内含量最高，其次为胞膜。Gd和Ce使细胞内钙含量增加，促进细胞钙内流。结论①La3+对细胞有明显剂量-效应关系，在10-10(或10-9)～10-6mol/L剂量范围内有促进细胞增殖作用，在10-4～10-3mol/L时有细胞毒性作用。②REE可进入细胞，且在核内富集。③REE可促进细胞外钙进入细胞。