砷致癌机制的细胞分子生物学研究

目的　探讨砷致癌的细胞分子生物学机制。方法　建立砷诱导NIH3T3细胞转化模型。测定细胞液中谷胱甘肽 (GSH)、谷胱甘肽转移酶 (GST)和谷胱甘肽还原酶 (GR)水平 ,通过NorthernBlot测定GR和谷胱甘肽过氧化物酶 (GPx)的基因表达。结果　NIH3T3细胞在 0 1 μmol/LAs(Ⅲ )诱导的 1 1 0d后发生了细胞生物学改变 ,由体外有限传代变为无限传代 ,在半固体琼脂上可以每千个细胞形成 60个集落。GR和GST活性显著增高。结论　建立了可行的砷诱导体外细胞转换的模型 ,提出了在引起细胞转化的机制中GSH的水平的下降起了重要的作用 ,而GST和GR蛋白的上升也与此机制有关。

Molecular mechanism of carcinogenesis induced by arsenic

Objective To study molecular mechanism of carcinogenesis induced by arsenic.Methods A cell transformation model in NIH3T3 cell induced by a rsenic was set up to investigate the arsenic effect on glutathione (GSH),glutath ione-S-transferase (GST) and glutathione reductase (GR) levels.Protein express ions of GR and glutathione peroxidase (GPx) were determined by Northern Blot ass ay.Results After 110-days′treatment with 0 1 μmol/L As(Ⅲ),mal ignant transformation occurred in NIH3T3 cells characterized as morphological ch anges.Cell life became immortalized from 30～40 passages life and that cell may grow in soft agar and form large colony anchorage-independent growth,plating ef ficiency (colony per 1 000 cell) was 60 The GR and GST activity in treatment wi th arsenic was increased.Conclusion A feasible cell transformation model in NIH3T3 cell induced by arsenic has been established.The results showed that down-regulaion of GSH level was closely related to arsenic cytotoxicity,while up-regulation o f GST and GR protein levels related to cell malignant transformation induced by arsenic.