有机磷与拟除虫菊酯农药的拟雌激素活性研究

目的观察有机磷与拟除虫菊酯农药的拟雌激素活性.方法选用5种有机磷农药辛硫磷(Pho)、马拉硫磷(Mal)、乐果(Dim)、久效磷(Mon)和水胺硫磷(Opt)]和4种拟除虫菊醋农药氰戊菊酯(Fen)、溴氰菊酯(Del)、氯氰菊酯(Cyp)和苄氯菊酯(Per)],进行大鼠子宫雌激素受体(ER)竞争结合试验和人乳腺癌MCF-7细胞增殖试验.结果 5种有机磷农药在体外均不与大鼠子宫ER结合,不能诱导MCF-7细胞增殖;4种拟除虫菊酯农药在体外能与2,4,6,7-3H雌二醇(3H-E2)竞争ER,其结合能力Fen＞Cyp＞Per＞Del,Fen与Cyp抑制3H-E2与ER结合的IC50分别为0.479、0.562 mmol/L;拟除虫菊酯能引起MCF-7细胞不同程度的增殖,刺激增殖能力Per＞Fen＞Del＞Cyp,其中Cyp、Del和Per所引起的增殖效应能被雌激素拮抗剂ICI 178.820完全阻断,而Fen所引起的细胞增殖不能被完全阻断.结论观察的5种有机磷农药不具有拟雌激素活性;4种拟除虫菊酯农药通过激活ER显示其拟雌激素活性.Fen诱导的MCF-7细胞增殖不完全是由ER激活所引起.

Research on the estrogenicity of organophosphorus and pyrethroid pesticides

Objective To observe the estrogenicity of organophosphorus and pyrethroid pesticides. Methods Five organophosphorus pesticidesphoxim(Pho),malathion(Mal),dimethoate(Dim),moncrotophos(Mon) and optunal(Opt)] and four pyrethroid pesticidesfenvalerate(Fen),cypermethrin(Cyp),permethrin(Per) and deltamethrin(Del)] were selected to perform estrogen receptor(ER) binding assay and human breast cancer MCF-7 cell proliferation assay. Results All of the organophosphorus pesticides were unable not only to bind to rat uteri ER but also to induce the proliferation of human breast cancer MCF-7 cell.The four pyrethroid pesticicdes were able to bind to the rat uteri ER through competing against 2,4,6,7- 3H]oestradiol( 3H-E 2) in vitro,the binding potentials were Fen>Cyp>Per>Del,of which IC 50 of the Fen and Cyp inhibiting 3H-E 2 from binding to ER were 0.479 mmol/L and 0.562 mmol/L respectively.All of the pyrethroid pesticides were able to stimulate the proliferation of MCF-7 cell to varying extent,the order of their abilities to induce the proliferation were listed as follows:Per>Fen>Del>Cyp.The cell proliferations induced by Cyp,Per and Del could be blocked by estrogen antagonist ICI 178.820,while that by Fen could be only partly blocked. Conclusions In the present study,the above organophosphorus pesticides selected do not show any estrogenicity,while the pyrethroid pesticides exhibit the estrogenicity through binding and activating ER.However,besides ER activation,there may be other mechanism in the Fen-induced MCF-7 cell proliferation.