中文摘要：

目的探讨活化蛋白-1（activated protein-1，AP-1）在苯并（a）芘[benzo（a）pyrene，S（a）P]引起的人胚肺成纤维细胞（HELF）周期改变中的作用以及AP．1与细胞周期蛋白D1（cyclinD1）、细胞周期蛋白依赖激酶4（CDK4）和E2F-1／4的上下游关系。方法转染AP-1荧光报告质粒的HELF细胞（AP-H）无血清培养48h后，加入2μmol／LB（a）P作用24h，用荧光检测法检测AP-1的相对活性。用AP-1的化学抑制剂姜黄素（curcumin）抑制其活性，观察它与cyclin D1／CDK4和E2F-1／4的上下游关系。采用流式细胞仪检测细胞周期的变化，用Western blot检测细胞中cyclin D1、CDK4和E2F-1／4蛋白水平的改变。结果2μmol／LB（a）P作用24h后，G1期细胞比例由（71±2）％减少为（48±3）％，差异有统计学意义（P〈0．05）；AP-1的活性增加；cyclin D1／E2F-1的蛋白含量增加；CDK4／E2F-4的蛋白水平没有明显改变。抑制AP-1活性后，B（a）P诱导的细胞周期的改变被逆转，B（a）P诱导的cyclin D1／E2F-1蛋白含量的增加被抑制，CDK4／E2F-4蛋白含量没有明显改变。结论S（a）P通过AP-1引起HELF周期的改变。AP-1是cyclin D1／E2F-1的上游信号分子，但对CDK4／E2F-4的表达不具有调节作用。

英文摘要：

Objective To investigate the roles of activated protein 1 （AP-1 ）in cell cycle changes on human embryo lung fibroblasts （ HELF ） induced by be nzo （a） pyrene [B （a） P], and relationships between AP- 1 and cychn D1/CDKg-E2F-1/4. Methods Cells transfected with AP-1 luciferase reporter plasmid（AP-H） were cultured with serum-free RPMI 1640 for 48 h, and treated with 2 μmol/L B（a ）P for 24 h. AP-1 relative activity was detected by luciferase assay. Changes of cell cycle and the expression of cyclin D1 ,CDKg and E2F-1/g were checked using the flow cytometer and Western blot assay. Results After B（a）P was treated for 24 h ,the ratio of G1 phase cells（71±2 ）% was decreased to （48±3）% （P〈0.05）,and an increase was observed in the ratio of S phase. AP-1 activity and cyclin D1/E2F-1 expression were increased significantly, but C DKg/E2F-4 expression did not change after B（a）P treatment. When AP-1 activity was inhibited by curcumin,decreases of G, phase in response to B （a）P treatment were blocked,and overexpression of cyclin D1/E2F-1 was attenuated,but CDKg/E2F-4 expression was not changed significantly. Conclusion AP-1 is involved in B （a）P induced cell cycle changes, and is the upstream signals of cyclin D1/E2F-1, but not CDK4/E2F-4.