中文摘要：

目的 研究苯并（a）芘（BaP）对人胚肺成纤维细胞（HELF）的细胞周期分布及丝裂原活化蛋白激酶（MAPK）信号分子（ERK1／2、JNK1／2和p38）磷酸化水平的影响，并探讨MAPK磷酸化水平改变与细胞周期效应之间的关系。方法 用0．1、0．5、2．5和12．5μmol／L的BaP处理HELF细胞24h，用蛋白印迹方法检测ERK1／2、JNK1／2和p38蛋白激酶的磷酸化水平和蛋白总量的改变，利用流式细胞技术检测2．5μmol／LBaP处理24h后对HELF细胞周期的影响。结果 不同剂量BaP可明显提高ERK1／2、JNK1／2和p38蛋白激酶磷酸化水平；2．5μmol／LBaP处理24h，细胞周期分布与二甲基亚砜对照组相比，G0与G1期细胞数下降了11．9％（F=41．38，P〈0．01），S期细胞数增加了17．2％（F=68．13，P〈0．01）；三种MAPK化学抑制剂（AG126、SP600125及SB203580）可明显抑制BaP处理引起的细胞周期的改变。结论 ERK1／2、JNK1／2和p38均参与了BaP所致细胞周期改变过程．并发挥币性调节作用。

英文摘要：

Objective To study the effects of benzo （a） pyrene （ BaP ） on the cell cycle distribution and activities of mitogen-activated protein kinase （MAPK） signal molecules （ ERK1/2, JNK1/2 and p38） in human embryo lung cells （HELF）, and to investigate the relationship between alterations of MAPK protein phosphorylation and the cell cycle distributions. Methods The phosphorylation of MAPK were induced by exposing HELF cells to BaP at 0. 1,0. 5, 2. 5 and 12. 5 μmol/L The phosphorylation and protein expression levels of ERK1/2, JNK1/2 and p38 were determined through western-blotting assay. And the flow cytometry assay was used to measure the cell cycle effects in HELF cells after treatment with 2. 5μmol/L BaP for 24 h. Results The phosphorylation levels of ERK1/2, JNK1/2 and p38 were significantly increased through BaP exposure. In addition, the phosphorylation of these three MAPKs has similar alteration pattern. We found that exposure of cells to 2. 5 μM of BaP for 24 h resulted in a decrease of Go and G1 population by 11.9% （F =41.38 ,P 〈0. 01 ） and an increase of S population by 17. 2% （F = 68. 13, P 〈 0. 01 ） . Three chemical inhibitors of MAPK （ AG126, SP600125 and SB203580 ） could significantly inhibit the cell cycle alteration because of BaP treatment. Condusion ERK1/2, JNK1/2 and p38 could positively regulate the BaP independently induced cell cycle alterations.