Study On Enantioselectivity In Estrogenic Activity For Pyrethroid Pesticides

Despite the fact that the biological process of chiral compounds are enantioselective,the endocrine disruption activity and uptake of chiral compounds with respect to enantioselectivity has so far received limited research.To study the estrogenic effects of commonly-used pyrethroid pesticides on the proliferation of MCF-7 cells.Five pyrethroid pesticides such as cyhalothrin,tetramethrin,permethrin,beta-cypermethrin and bifenthrinwere selected to perform human breast cancer MCF-7 cell proliferation assay.And the differences of endocrine-disrupting in enantiomers of beta-cypermethrin,bifenthrin were studied.To study the estrogenic effects of commonly-used pyrethroids pesticides on the expression of the estrogen receptor(ER)gene and pS2 gene.bifenthrin were selected to perform transcription activation assay.The proliferative status was assayed by MTT and the mRNA levels determined by real-time quantitative PCR.All of the pyrethroid pesticides(cyhalothrin(Cyh),tetramethrin(Tet),permethrin(Per),beta-cypermethrin(β-Cyp)and bifenthrin(BF))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 follow: Per＞BF＞Cyh＞β-Cyp＞Tet.The result means that the pyrethroid pesticides selected exhibit estrogenicity.β-Cyp were got from cypermethrin through epimerization.The disrupting effects of endocrine-disrupting mainly come from enantiomerics (1R-cis-αS,1R-trans-αS,1S-cis-αR).The enantiomeric such as 1S-Trans-αR has the high insecticidal activity,but the disrupting effects of endocrine-disrupting is very weak,significantly lower than the other three enantiomers with a significant difference(P＜0.05,P＜0.01).The cell proliferation induced by the fourβ-Cyp enantiomers may be through the classical estrogen response pathway via the estrogen receptor(ER),as the proliferation induced by the enantiomers could be completely blocked when combined with 10^-6mol/L of the ER antagonist ICI 182.780.In the E-SCREEN assay,the disrupting effects of endocrine-disrupting mainly come from enantiomeric 1S-cis-BF.enantiomeric such as 1R-cis-BF has the high insecticidal activity,but the disrupting effects of endocrine-disrupting is very weak,significantly lower than the other enantiomer 1R-Cis-BF with a significant difference(P＜0.01).The mRNA levels determined by real-time quantitative PCR.The pS2 mRNA level induced by 1S-cis-BF is higher than 1R-cis-BF.The down-regulation of ERαmRNA expression induced by 1S-cis-BF is higher than 1R-cis-BF.The order of their abilities to induce the proliferation was listed as follow: 1S-cis-BF＞1R-cis-BF.This suggests that the cell proliferation induced by BF may be through the classical estrogen response pathway via the estrogen reeeptor(ER).