DDT类农药同分异构体和同系物的联合雌激素效应

A Study on the Combined Estrogenic Effects of the Isomers and the Homologue of DDT Pesticide

[目的]研究DDT类农药同分异构体和同系物的联合雌激素效应。[方法]用重组人雌激素受体（hER）基因酵母细胞（W303—1A／hER—ERE—LacZ）评价DDT农药同分异构体和同系物的雌激素活性。将终浓度为10^-4-10^-15的17β-雌二醇、终浓度为10^-3-10^-9的p，p＇-DDT、o，p＇-DDT和p，p＇-DDD、p，p＇-DDE加入酵母细胞培养液，作用4h，通过定量测定β-半乳糖苷酶的活性表示DDT农药的雌激素作用强度。[结果]o，p-DDT和p，p＇-DDD能像配体一样与hER结合，发挥雌激素效应，并且具有剂量效应关系，回归方程分别为^y=1．4553x^2＋47．366x＋333．31和^y=-0．1658x^3．6506x^2—23．176x-25．809。同分异构体间比较，o，p＇-DDT相对雌激素活性较强，EC50为2．04×10^-7mol／L，而p，p-DDT的EC50为3．71×10^-4mol／L，两者雌激素作用呈协同效应，联合效应相加指数（AI）=0.74（〉0）；同系物间比较，P，P＇-DDD雌激素活性明显较强，EC50为2．78×10^-7mol／L，而p，p＇-DDE的EC50为5．88×10^-5mol／L，两种同系物的雌激素作用呈拮抗效应．AI=-1．13（〈0）。[结论]o，p-DDT和p，p＇-DDD是经雌激素受体（ER）介导的环境雌激素，o，p-DDT与p，p＇-LDDT同分异构体间雌激素活性具有协同效应，p，p-DDD和p，p-DDE同系物间雌激素活性呈拮抗效应。

[ Objective ] To study the combined estrogenic effects of the isomers and the homologue of DDT pesticide. [ Methods ] Using a recombinant human estrogen receptor gene yeast cell to assess the estrogenic activity of isomers and the homologue of DDT pesticides. The different concentrations of 17β -estradiol and individual DDT isomers and homologue such as p, p＇-DDT, o, p＇-DDT, p, p＇-DDD and p, p＇-DDE and their mixtures were added to yeast cuhures, and then estrogenic activity was measured by quantification of β -galactosidase after 4 hours culture. [ Results ] o, p＇-DDT and p, p＇-DDD have the ability to play an estrogenic effects to bind hER like a ligand and a dose dependent model existed between the estrogenic effects and the DDT concentration; the regression equations are ^y = 1.4553x^2 ＋ 47.366x ＋ 333.31 and ^y = -0.1658x^3-3.6506x^2-23.176x -25.809 respectively. Compared with that of p, p＇-DDT isomer with its EC50 3.71 × 10^-4 mol/L, the relative activity of o, p＇-DDT with its EC50 2.04 × 10^-7 mol/L was more estrogenic, and the estrogenic effects of isomers showed a synergism, AI=0.74（ 〉0 ）. p, p＇-DDD was more estrogenic with its EC50 2.78 × 10^-7 mol/L compared top, p ＇-DDE with its EC50 5.88× 10^-5 mol/L, and an antagonism was shown between the homologues, AI=-1.13 （ 〈0 ）. [ Conclusion ] o, p＇-DDT and p, p＇-DDD are environmental estrogen mediated by ER. The joint estrogenic effect of isomers, p, p＇-DDT, o, p ＇-DDT showed synergic, and that of homologues, p, p ＇- DDD andp, p＇-DDE, showed antagonistic respectively.