杀螟硫磷体外环境雌激素活性及机制研究

Study on environmental estrogenic activity of fenitrothion in vitro and its mechanism

目的 检测杀螟硫磷的环境雌激素活性，并探讨其作用机制。方法 人乳腺癌细胞株（MCF-7）细胞在含10％小牛血清的RPMI1640培养基中进行半开放式贴壁培养，加受试物前2周，改在含10％去激素小牛血清的无酚红RPMI1640培养基中培养。试验设溶剂对照组、阳性对照组及杀螟硫磷5个不同浓度实验组，采用MCF-7细胞增殖试验、四甲基偶氮噻唑蓝（MTT）试验和生长曲线观察杀螟硫磷对MCF-7细胞增殖的影响，并通过雌激素受体（ER）结合试验分析杀螟硫磷与ER的结合情况。结果 杀螟硫磷在10^-9～10^-6mol／L剂量范围内可诱导MCF-7细胞增殖，差异有统计学意义（P〈0．05），且存在剂量-效应关系。杀螟硫磷能与ER结合，抑制^125I-E2与ER结合。结论 杀螟硫磷具有环境雌激素活性，其拟雌激素作用由ER介导而产生。

Objective To evaluate the environmental estrogenic activity of the pesticide fenitrothion and study the possible mechanism. Methods Human breast cancer cell strain MCF-7 cells were maintained in RPMI1640 medium containing 10% bovine serum. Two weeks before the addition of Fenitrothion, the cells were transformed into phenol red-free RPMI1640 medium containing 10 % charcoal/dextran treated bovine serum. There were seven groups, vehicle control group, positive group and five Fenitrothion groups. MCF-7 cells proliferation test, MTT test and growth curve were used to assess the effect on the proliferation of MCF-7 cells by fenitrothion and estrogen receptor（ER） binding test was used to analyze the binding ability of fenitrothion with ER. Results Fenitrothion could induce the proliferation of MCF-7 cells at 10^ - 7 mol/L 10^- 5 mol/L with dose-effect relationship, and this effect was significantly different from the vehicle control（ P 〈 0.05 or P 〈 0.01）. Fenitrothion could bind with ER and inhibit the bind of ^125I-E2 with ER. Conclusion Fenitrothion has environmental estrogenic activity which was mediated by ER.