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目的阐明辐射致癌过程中肿瘤坏死因子α(TNFα)的作用及蛋白质酪氨酸磷酸化调节机理。方法以05Gyα粒子照射的叙利亚地鼠胚胎(SHE)细胞为靶细胞,观察细胞生长曲线、转化频率(TF)、软琼脂克隆形成率(CFE)和裸鼠致瘤性,并测定细胞中蛋白质酪氨酸激酶和酪氨酸磷酸酶活性。结果单纯0.5Gyα粒子照射或TNFα不能使SHE细胞发生恶性转化,600U/mlTNFα处理0.5Gyα粒子照射的SHE细胞后,细胞获得了长期传代的能力,TF、CFE以及细胞中蛋白质酪氨酸磷酸化水平均明显增高,裸鼠致瘤性试验为阳性。结论TNFα对α粒子致SHE细胞转化有显著促进作用,且该过程中可能涉及蛋白质酪氨酸磷酸化的调控机制
Objective To elucidate the role of tumor necrosis factor-α (TNF-α) and regulation mechanism of protein tyrosine phosphorylation during radiation carcinogenesis. METHODS: Syrian hamster embryo (SHE) cells irradiated with 0.5% Gyα particles were used as target cells to observe the cell growth curve, transformation frequency (TF), soft agar colony formation rate (CFE) and tumorigenicity in nude mice, and the cells were assayed. Protein tyrosine kinase and tyrosine phosphatase activity. Results Single 0.5 Gy alpha particle irradiation or TNF alpha could not cause the malignant transformation of SHE cells. After treatment with 600 U/ml TNF alpha with 0.5 Gy alpha particle-exposed SHE cells, the cells had long-term ability to pass, TF, CFE and protein in the cells. Tyrosine phosphorylation levels were significantly higher and the tumorigenicity test in nude mice was positive. Conclusion TNFα can significantly promote the transformation of SHE cells induced by α-particles, and the regulation of protein tyrosine phosphorylation may be involved in this process.