| 18700809 |
Wang L, Zhou S, Lin K, Zhao M, Liu W, Gan J: Enantioselective estrogenicity of o,p'-dichlorodiphenyltrichloroethane in the MCF-7 human breast carcinoma cell line. Environ Toxicol Chem. 2009 Jan;28(1):1-8.
Research increasingly suggests that selectivity between enantiomers may exist in acute and chronic toxicological effects of chiral contaminants. In this study, we used the human breast carcinoma MCF-7 cell line to evaluate enantioselectivity of o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT). Baseline separation of o,p'-DDT enantiomers was achieved on the Chiralcel OJ chiral column by high-performance liquid chromatography, and the absolute configuration and optical rotation of the resolved enantiomers were further identified. Significant differences in estrogenic potential were observed between the two enantiomers of o,p'-DDT in the MCF-7 cell proliferation assay (i.e., the E-Screen assay) and the real-time quantitative polymerase chain reaction (PCR). In the E-Screen assay, the relative proliferative effect ratios of R-(-)-o,p'-DDT and S-(+)-o,p'-DDT were 89.4 and 27.9%, respectively, and the relative proliferative potency ratios were 0.1 and 0.001%, respectively. Compared to the solvent control, R-(-)-o,p'-DDT induced the maximal increase of 2.31-fold at a concentration of 10 (-6) mol/L, while S-(+)-o,p'-DDT at 10 (-5) mol/L induced the maximal increase of 1.65-fold in estrogenic biomarker pS2 mRNA level. The maximal down-regulation of the transcription levels of estrogen receptor alpha (ERa) and ER3 by R-(-)-o,p'-DDT were 49 and 40% at the concentration of 10 (-6) mol/L, while those by S-(+)-o,p'-DDT were 24 and 26% at the concentration of 10 (-5) mol/L. The cell proliferation, the up-regulation of pS2, and the down-regulation of ERalpha and ERbeta gene expressions induced by the racemate and enantiomers of o,p'-DDT were all reversed by cotreatment with 10 (-6) mol/L ICI 182,780. Therefore, the enantioselective estrogenicity of o,p'-DDT was likely through the ERalpha and ERbeta signaling pathways. Results from this study suggest the need for considering enantioselectivity of chiral contaminants in chronic ecological toxicities. |
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