镍化合物致人胚肺细胞转化及细胞周期的研究

Studies on cell transformation and cell cycle in human embryo lungs induced by nickel compounds

目的 探讨镍化合物与职业性肺癌的关系。方法 用水不溶性氧化镍和二硫化三镍体外转化人胚肺细胞 (MRC 9和IMR 90 ) ,并用流式细胞术分析这些转化细胞的细胞周期改变。结果 细胞在染毒 3～ 5个月后 ,MRC 9和IMR 90细胞均被诱发形态转化 ,包括转化灶的形成、无序重叠交叉生长和类上皮细胞化等。并且有的转化细胞能在软琼脂培养基中生长并形成集落。流式细胞术分析发现 ,转化细胞细胞周期发生改变。如未处理的MRC 9细胞 ,G1期为 6 2 6 1% ,G2 /M期只有16 37% ,几乎未见多倍体细胞 ,而在转化细胞中 ,G1期降到 5 0 %左右 ,G2 /M期超过 2 0 % ,多倍体细胞有的超过 10 %。在IMR 90细胞中也是如此。结论 水不溶性镍化合物可诱导人胚肺细胞形态转化 。

Objective To elucidate the association between nickel compounds and occupational lung cancer. Methods Human embryo lung cells (MRC 9 and IMR 90) were transformed by water insoluble nickel oxide and nickel subsulfide, and changes in cell cycle of these transformed cells were analyzed by flow cytometric technique. Results Morphological transformation in MRC 9 and IMR 90 cells were induced after exposure to nickel compounds for 3 5 months, including formation of transforming foci, overlaying growth and epithelium like changes in cells, etc. Some transformed cells could form colonies in soft agar media. Changes in cell cycle of the transformed cells were observed with flow cytometry. Proportions of cells at G 1 phase and G 2/M phase were 62 61% and 16 37%, respectively, in the untreated MRC 9 cells and hyperploid cells were hardly seen in cell cycle plots. But, in the transformed MRC 9 cells, proportion of cells at G 1 phase reduced to about 50%,and that at G 2/M phase increased to over 20% and that of hyperploid cells to over 10%. The same phenomenon was observed in the IMR 90 cells. Conclusions Water insoluble nickel compounds can induce morphological transformation of human embryo lung cells and those transformed cells appeared certain biological characteristics of tumor cells.