癌变·畸变·突变 ›› 2009, Vol. 21 ›› Issue (3): 210-213.doi: 10.3969/j.issn.1004-616x.2009.03.013

• 论著 • 上一篇    下一篇

活化蛋白-1在硒拮抗砷致细胞周期改变中的作用

王艺陪1,2, 李晓暖1, 来瑞平1, 余日安3, 鲁文清1,   

  1. 1.华中科技大学同济医学院公共卫生学院劳动卫生与环境卫生学系，教育部环境与健康重点实验室，湖北　武汉　430030；2. 上海大学环境与化学工程学院污染与健康研究所，　上海　200444； 3. 广东药学院公共卫生学院劳动卫生与环境卫生学系，广东　广州 510310
  • 收稿日期:2008-12-12 修回日期:2009-02-03 出版日期:2009-05-30 发布日期:2009-05-30

The Antagonism of Selenium on Arsenic-induced Cell Cycle Changes by Activator Protein-1 Regulation

WANG Yi-pei1,2, LI Xiao-nuan1, LAI Rui-ping1,YU Ri-an3, LU Wen-qing1,   

  1. 1. Department of Occupational and Environmental Health, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
  • Received:2008-12-12 Revised:2009-02-03 Online:2009-05-30 Published:2009-05-30

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摘要： 背景与目的： 研究激活蛋白1(activator protein-1, AP-1)在硒拮抗砷致细胞周期改变中的作用。 材料与方法： 以小鼠皮肤JB6-CI41细胞为靶细胞，分别用亚硒酸钠(2.5 μmol/L)和不同浓度的亚砷酸(3.125、6.25和12.5 μmol/L)单独及联合染毒JB6-CI41细胞，并用AP-1特异化学抑制剂姜黄素(20 μmol/L)与亚砷酸(12.5 μmol/L)联合染毒细胞，实验同时设生理盐水溶剂对照。上述各组染毒 2 h后收获细胞，用凝胶阻滞电泳技术(electrophoretic mobility shift assay，EMSA)检测细胞AP-1的DNA结合活性，用流式细胞仪检测细胞周期的变化。观察砷诱导细胞周期改变与AP-1的DNA结合活性之间的关系。 结果： 与溶剂对照相比，各浓度的亚砷酸均可引起JB6-CI41细胞AP-1的DNA结合活性显著增加(P<0.01)和G1期比率显著性减少(P<0.01)，较高浓度的亚砷酸(6.25和12.5 μmol/L)引起G2期比率增多(P<0.05,P<0.01)，2.5 μmol/L亚硒酸钠对AP-1的DNA结合活性和细胞周期均无显著影响(P均>0.05)。亚硒酸钠与亚砷酸联合作用时，与对应浓度的亚砷酸单独作用相比，JB6-CI41细胞的AP-1的DNA结合活性明显降低(P<0.01)，G1比率明显增多(P<0.01)，G2期比率显著减少(P<0.05)。AP-1抑制剂姜黄素与亚砷酸联合染毒与对应的亚砷酸单独染毒组相比，AP-1的DNA结合活性明显降(P<0.01)，G1期比率增高(P<0.01)而G2期比率降低(P<0.01)。 结论： 砷通过激活AP-1通路影响细胞周期的变化；硒在一定浓度下能够通过拮抗砷对AP-1的活化而抑制砷引起的细胞周期变化，这可能是硒拮抗砷致癌作用的机制之一。

关键词: 砷, 硒, AP-1, 细胞周期, 致癌作用

Abstract: BACKGROUND AND AIM: To explore the effect of selenium on arsenic-induced cell cycle changes by regulation of activator protein-1 (AP-1). MATERIALS AND METHODS: JB6-CI41 cells were exposed to sodium selenite alone at the concentrations of 2.5 μmol/L or combined with arsenous acid at the concentrations of 3.125, 6.25, and 12.5 μmol/L. The AP-1 DNA binding activity and cell cycle were analyzed by electrophoretic mobility shift assay (EMSA) and flow cytometry. Meanwhile, curcumin (20 μmol/L), a specific inhibitor of AP-1, was used to treat JB6 cells together with arsenous acid(12.5 μmol/L) in order to understand the relationship between arsenic-induced cell cycle changes and AP-1 DNA binding activity. RESULTS: Compared with solvent control, arsenous acid (3.125, 6.25 and 12.5 μmol/L) could significantly up-regulate AP-1 DNA binding activity and reduce G1 phase cells (P<0.01,P<0.01), and higher concentrations of arsenous acid (6.25 and 12.5 μmol/L) increased G2 phase cells (P<0.05,P<0.01). Sodium selenite (2.5 μmol/L) showed no effect on AP-1 DNA binding activity and cell cycle(P>0.05,P>0.05). Compared with corresponding concentrations of arsenous acid, co-exposure of JB6-CI41 cells to sodium selenite (2.5 μmol/L) and arsenous acid (3.125,6.25 and 12.5 μmol/L) down-regulated AP-1 DNA binding activity (P<0.01), increased G1 phase cells (P<0.01), and decreased G2 phase cells (P<0.05). Co-exposure of JB6-CI41 cells to curcumin and arsenous acid could significantly down-regulate AP-1 DNA binding activity, increased G1 phase cells and decreased G2 phase cells compared with corresponding concentrations of arsenous acid(all P<0.01). CONCLUSION: Arsenic may change cell cycle by activating AP-1 signal pathway. Certain concentration of selenium could down-regulate arsenic-induced AP-1 DNA binding activity, which may be one of the mechanisms that selenium could antagonize the carcinogenetic property of arsenic.

Key words: selenium, arsenic, activator protein-1, cell cycle, carcinogenesis

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