NiCl2诱导人支气管上皮细胞系恶性转化的研究

目的 建立NiCl2诱导永生化人支气管上皮细胞系(16HBE)恶性转化的模型，为下一步关于镍化合物致癌的分子机制的研究提供相应的恶性转化细胞。方法 通过克隆形成率实验确定NiCl2诱导16HBE细胞转化浓度后，对16HBE细胞进行分阶段多次染毒，每隔20d染毒1次，每次染毒24h。染毒12次后，通过软琼脂集落形成试验和裸鼠体内致瘤试验鉴定细胞恶性转化程度。结果 经NiCl2多次处理，16HBE细胞至75代时，细胞生长速度加快，排列紊乱，失去接触抑制，出现复层生长，并可在软琼脂上生长，且呈剂量一反应关系，但在第75代之前的细胞则不能在软琼脂上生长。转化细胞在裸鼠体内成瘤，病理组织学证实为低分化鳞状细胞癌。结论NiCl2具有使16HBE细胞发生恶性转化的能力。

Study on Malignant Transformation of Bronchial Epithelial Cell Induced by NiCl2

Objective In order to explore the molecular mechanism of nickel carcinogenesis,to establish a malignant transformation model for human bronchial epithelial cell(16HBE)with nickel chloride.Methods 16HBE cells were treated 12 times with an interval of 20 days with nickel chloride of different concentrations in vitro.The cell features of malignant transformation were identified by colony forming frequency on soft agar and test of tumorigenesis is nude mice.Results Cells of the 75 th generation proliferated rapidly and exhibited in extensive random orientation and crossover growth.Compared with the negative control cell,the efficiency of colony formation for transformed cells in semi solid agar increased significantly and dose dependently.However,cells prior to the 75 th generation were not able to grow in semi solid agar.Transformed cells could form subcutaneous tumor in nude mice.The tumors were poor differentiated squamous cell carcinoma in morphology confirmed by histopathological examination.Conclusions Nickel chloride could induce malignant transformation of 16HBE cells.