外源雌激素的低剂量非线性效应研究进展

Research advance in low-dose and nonmonotonic effects of xenoestrogens

从传统意义上看,任何物质只要达到一定数量或浓度都会对机体产生毒性,而低于安全阈值则不具有相应的毒性。毒理学研究认为高剂量的化学物质可对生物体产生生物毒性效应,而最新研究则表明外源雌激素(xenoestrogens,XEs)可在不同组织水平表现出双向剂量效应(倒"U"型),尤其表现为低剂量非线性效应。XEs是一类典型的环境内分泌干扰物,其主要通过模拟或干扰体内正常雌激素的合成、代谢和转运,从而干扰正常的生物内分泌功能。XEs通过基因组途径和非基因组途径的联合作用产生低剂量非线性效应。本文综述了XEs在生物个体及细胞分子水平的低剂量非线性效应,阐述了XEs低剂量非线性效应的产生机理,介绍了环境痕量XEs的检测分析方法。在此基础上,对XEs低剂量非线性效应今后的研究方向进行了展望,以期为XEs环境生态安全和人体健康研究提供理论指导。

In the traditional sense,any material may produce biotoxicity as long as it reaches a certain quantity or concentration,while it doesn＇t have the corresponding toxicity when it is lower than the safe threshold. For many years,toxicologists have believed that higher doses of chemicals will cause greater effects than lower doses,while multiple researches on xenoestrogens（ XEs） have demonstrated that XEs are capable of eliciting biphasic dose responses（ inverted U shape curve） with different endpoints at many organization levels,especially inducing low-dose and nonmonotonic interference effects. XEs are a class of typical environmental endocrine disruptors（ EDCs）,leading to disturbance of normal endocrine function mainly through simulating or interfering with the synthesis,metabolism and transport of body＇s normal endogenous estrogen.XEs induce low-dose and nonmonotonic effects by the combination of genomic and non-genomic pathways. This paper summarized the low-dose estrogenic effects of XEs on individual organism and molecular cell levels. The estrogenic effect mechanisms（ i. e.,genomic and non-genomic effects） were presented,and the analysis methods of environmental XEs trace concentrations were described. Finally,the future research direction of the low-dose and nonlinearity effects was prospected,providing theoretical guidance for ecological safety and human health research of XEs.