中文摘要：

目的探讨细胞周期蛋白D1（cyclinD1）／细胞周期蛋白依赖激酶4（CDK4），E2F-1／4通路在苯并（a）芘[B（a）P]引起的人胚肺成纤维细胞（HELF）周期改变中的作用。方法分别用2μmol／L的B（a）P作用HELF24h和100μmol／LB（a）P作用3次，每次24h，细胞具有转化细胞的部分特征（THELF）。用转染反义cyclinD1和CDK4质粒的HELF（A-D1，A-K4）和T-HELF（T-A-D1，T-A-K4）研究cyclinD1／CDK4与E2F-1／4的上下游关系。用流式细胞仪和Western blot法检测细胞周期、cyclin D1、CDK4和E2F-1／4蛋白表达的改变。结果2μmol／LB（a）P作用24h HELF中G1期细胞数明显减少。在A-D1和A-K4的HELF中，cyclinD1和CDK4表达的抑制阻断了由B（a）P引起的细胞周期从G1期进入S期的变化。B（a）P刺激后HEIF中cyclinD1和E2F-1的表达明显增加。在A-D1中，E2F-1的高表达被抑制。B（a）P作用A-K4细胞后，CDK4表达明显升高，E2F-4表达明显降低。T-A-D1和T-A-K4的T-HELF多数停留在G1期。与HELF相比，T-HELF中cyclin D1的表达明显增加；与T-HELF相比，T-A．D1和T-A-K4中E2F-4表达明显增加。结论在2μmol／L B（a）P作用的HELF中，B（a）P通过cyclinD1／CDK4-E2F-1／4信号转导通路引起细胞周期的改变。在T-HELF中，B（a）P通过cyclinD1／CDK4-E2F-4信号转导通路引起细胞周期的改变。

英文摘要：

Objective To investigate the roles of cyclin D1/CDK4-E2F-1/4 pathway in cell cycle changes of human embryo lung fibroblasts （HELF） induced by two different benzo（a） pyrene [ B（a） P] treatment models. Methotls Two B（a）P treatment models： HELF were treated by 2μmol/L B（a）P for 24 hours; HELF were treated by 100 μmol/L B（a）P three times 24 hours each and provide with some characteristics of transformed cells （THELF）. Changes of cell cycle and the expression of cyclin D1, CDK4 and E2F-1/4 were checked using the flow cytomter and Western bolt analysis. Results After 24 hours 2μmL/L B（a）P treatment,the HELFs in the G1 phase was decreased. In HELF transfected with antisense cyclin D1 （A-D1） and antisense CDK4 （A-K4）, the expression of cyclin D1 and CDK4 blocked the cell cycle changes from the G1 phase to the S phase induced by B（a）P. The overexpression of cyclin D1 and E2F-1 in HELF was induced by B（a）P. The E2F-1 overexpression in A-D1 induced B（a） P was inhibited. The E2F-4 expression was decreased and the CDK4 expression was increased significantly in A-K4 after B（a）P treatment.Most of T-HELF Iransfected with antisense cyclin D1 （T-A-D1） and antisense CDK4 （T-A-K4） were retained in Ga phase. The cyclin D1 expression in T-HELF＊was increased significantly compared with that in HELF.The E2F-4 expression in T-A-D1 and T-A-K4 was increased signiticantly compared with that in T-HFZF. Conclusion B（a） P induces the cell cycle changes through cyclin D1/CDK4-E2F-1/4 pathway in HELF treated by 2μmol/L B（a）P while it induces cell cycle changes through cyclin D1/CDK4-E2F-4 pathway in T-HELF.