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ABSTRACT: Dichlorodiphenyltrichloroethane (DDT) is ubiquitous in the environment, and the exposure to DDT and its related pesticides has long been linked to endocrine disruption. The mechanism of endocrine disruption toward targeted receptors, however, remains unclear. Probing the molecular recognition of DDT analogs by targeted receptors at the atomic level is critical for deciphering this mechanism. Molecular dynamics (MD) simulations were applied to probe the molecular recognition process of DDT and its five analogs, including dichlordiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), methoxychlor (MXC), p,p'-hydroxy-DDT (HPTE), and dicofol by human estrogen receptor (ER) α and human ER-related receptor (ERR) γ. Van der Waals interactions mainly drive the interactions of DDT analogs with ERα ligand-binding domain (LBD) and ERRγ LBD. Minor structural changes of DDT analogs in the number and position of chlorine and phenolic hydroxyl moiety cause differences in binding modes through aromatic stacking and hydrogen bonding and thus affect differently conformational changes of ERα LBD and ERRγ LBD. The binding of DDT analogs affects the helix 12 orientation of ERα LBD but causes no rearrangement of helix 12 of ERRγ LBD. These results extend our understanding of how DDT analogs exert their estrogen-disrupting effects toward different receptors via multiple mechanisms. Environ. Toxicol. Chem. 2012; 31: 2597-2605. © 2012 SETAC.
Environmental Toxicology and Chemistry 08/2012; 31(11):2597-605. · 2.81 Impact Factor
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ABSTRACT: A large portion of polychlorinated biphenyls (PCBs) from e-waste released into the coastal areas may be the potential source of PCBs to the global oceans. The paper presents data of PCBs concentrations in fifty surface sediment samples and a dated sediment core in Yangtze River Delta (YRE) and adjacent East China Sea (ECS). The total PCBs levels varied from 5.08 to 19.64 ng/g dry weight, with the highest concentrations situate within the river-sea boundary zone which is so-called "marginal filter". Concurrent with the operation of e-waste recycling over the last two decades, PCB fluxes started to rise again after 1980s and reached a maximum in this century. The full data set was used to estimate the burden of PCBs in YRE and adjacent ECS. A total sediment burdens were 192.8 tons, with the spatial density of 364 ng/cm(2) which accounts for 1.9% of all the PCBs in China.
Environmental pollution (Barking, Essex: 1987) 06/2012; 169:20-6. · 3.43 Impact Factor
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ABSTRACT: The continued uses of dichlordiphenyltrichloroethane (DDT) for indoor vector control in some developing countries have recently fueled intensive debates toward the global ban of this persistent legacy contaminant. Current approaches for ecological and health risk assessment has ignored the chiral nature of DDT. In this study by employing an array of cytotoxicity related endpoints, we investigated the enantioselective cytotoxicity of o,p'-DDT.
we demonstrated for the first time that R-(-)-o,p'-DDT caused more neuron cell death by inducing more severe oxidative stress, which selectively imbalanced the transcription of stress-related genes (SOD1, SOD2, HSP70) and enzyme (superoxide dismutase and lactate dehydrogenase) activities, and greater cellular apoptosis compared to its enantiomer S-(+)-o,p'-DDT at the level comparable to malaria area exposure (parts per million). We further elucidated enantioselective modes of action using microarray combined with enzyme-linked immunosorbent assay. The enantioselective apoptosis might involve three signaling pathways via caspase 3, tumor protein 53 (p53) and NF(k)B.
Based on DDT stereochemistry and results reported for other chiral pesticides, our results pointed to the same directional enantioselectivity of chiral DDT toward mammalian cells. We proposed that risk assessment on DDT should consider the enantiomer ratio and enantioselectivities.
PLoS ONE 01/2012; 7(8):e43823. · 4.09 Impact Factor
