乙酸镍对人支气管上皮细胞系的恶性转化研究

目的：建立乙酸镍(niekel acetate)对永生化人支气管上皮细胞系(16BHE)的恶性转化模型，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乙酸镍对16HBEK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鼠体内致瘤试验鉴定细胞恶性转化程度。结果：经乙酸镍多次处理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：乙酸镍具有使16HBE细胞发生恶性转化的能力。

STUDY ON THE ABILITY OF NICKEL ACETATE TO TRANSFORM 16HBE MALIGNANTLY

Purpose: To establish malignant transformed human bro nchial epithelial cell(16HBE) model by nickel acetate for explor ing deeply molecular mechanism of nickel carcinogenesis. Methods: 16HBE cells were treated twelve times(a time every 20 days) with nickel acetate of different concentration in vitro. The features of malignancy of transformed cells were identified by colony forming frequency on soft agar and test of tumorigene sis in nude mice. Results: The 75 th passage cells treated t welve times with nickel acetate proliferated rapidly and exhibit ed in an extensively random orientation. Compared with that of negative control cell, colony formation efficiency of transform ed cells in semisolid agar showed a significant increase and was dose_dependent. But before the 75 th passage, cells had n ot the ability of growth in semisolid agar. All the transfor med cells could formed tumor subcutaneously in the nude mice. The tumors were a poor differentiated squamous cell carcinoma in morphology confirmed by histopathological examination. Conclusi on: Nickel sulfide, nickel chloride and nickel acetate all cou ld induce malignant transformation of 16HBE cells.