Benzotriazole Ultraviolet Stabilizers Promote Breast Cancer Cell Proliferation via Activating Estrogen-Related Receptors α and γ at Human-Relevant Levels.

Benzotriazole ultraviolet stabilizers (BUVSs) are ubiquitous emerging pollutants that have been reported to show estrogenic disruption effects through interaction with the classic estrogen receptors (ERs) in the fashion of low activity. The present study aims at revealing the potential disruption mechanism via estrogen-related receptors α and γ (ERRα and ERRγ) pathways. By the competitive binding assay, we first found that BUVSs bond to ERRγ ligand binding domain (ERRγ-LBD) with Kd ranging from 0.66 to 19.27 µM. According to the results of reporter gene assays, the transcriptional activities of ERRα and ERRγ were promoted by most tested BUVSs with the lowest observed effective concentrations (LOEC) from 10 to 100 nM, which are in the range of human exposure levels. At 1 µM, most tested BUVSs showed higher agonistic activity toward ERRγ than ERRα. The most effective two BUVSs promoted the MCF-7 proliferation dependent on ERRα and ERRγ with a LOEC of 100 nM. The molecular dynamics simulation showed that most studied BUVSs had lower binding free energy with ERRγ than with ERRα. The structure-activity relationship analysis revealed that molecular polarizability, electron-donating ability, ionization potential, and softness were the main structural factors impacting the binding of BUVSs with ERRγ. Overall, our results provide novel insights into the estrogenic disruption effects of BUVSs.

The potential endocrine disruption mechanism of anthelmintic drug niclosamide by activating estrogen receptors and estrogen-related receptors.

Niclosamide (NIC), a helminthic drug used widely for controlling schistosomiasis, can reportedly disrupt the endocrine system. However, its underlying mechanisms are still unclear. In this study, we revealed the potential endocrine disruption mechanism of NIC by activating estrogen receptors (ERs) and estrogen-related receptors (ERRs). The binding potency of NIC with ERα, ERß and ERRγ were determined by fluorescence competitive binding assays, which shows an IC50 (the concentration of NIC needed to displace 50 % of the probe from the receptor) of 90 ± 4.1, 10 ± 1.7 nM and 0.59 ± 0.07 nM respectively. The IC50 for ERRγ is the lowest one among the three detected receptors, which is three orders of magnitude lower than the known agonist GSK4716.The transcriptional activities of NIC on ERs and ERRs were detected by MVLN cells (stably transfected with ERs reporter gene) and HeLa cells (transiently transfected with ERRs reporter gene)-based luciferase reporter gene assay. The lowest observable effective concentration (LOEC) ranked as follows: ERRγ (0.5 nM) < ERRα (10 nM) < ERs (100 nM). The maximum observed induction rate for ERRγ (294 %) was higher than that for ERRα (191 %). The maximum observed induction rate of NIC for ERs was 30 % relative to 17ß-estradiol. In addition, we simulated the interactions of NIC with ERs and ERRs by molecular docking. NIC could dock into the ligand binding pockets of ERs and ERRs and form hydrogen bonds with different amino acids. The binding energy ranked as follows: ERRγ (-8.90 kcal/mol) < ERß (-7.57 kcal/mol) < ERRα (-7.15 kcal/mol) < ERα (-6.53 kcal/mol), which implied that NIC bound to ERRγ with higher binding affinity than the other receptors. Overall, we clarify that ERRγ might be the dominant target for NIC in cells rather than ERRα and ERs. We reveal potential novel mechanisms for the endocrine disruption effects of NIC by activating both ERRs and ERs at environmentally-related nanomolar levels.

Bioaccumulation and human health risk assessment of DDT and its metabolites (DDTs) in yellowfin tuna (Thunnus albacares) and their prey from the South China Sea.

DDTs were detected in yellowfin tuna (Thunnus albacares, 92.1-221.8 ng‧g-1 lipid weight) and their prey (54.9-93.5 ng‧g-1 lipid weight) from the South China Sea (SCS). DDT levels reported in this study were lower than those of the previous studies indicated the recent mitigation of DDT contamination in the SCS. Higher DDT levels were observed in fat abdominal muscle than lean dorsal muscle in adult yellowfin tuna. Meanwhile, DDT levels in adult yellowfin tuna were higher than the young ones. The composition profiles of DDT and its metabolites suggested DDTs in fish in the SCS were mainly derived from the historical use of technical DDTs. DDTs were biomagnified through food chains with the trophic magnification factor of 2.5. Risk assessment results indicated that dietary exposure to DDTs through lifetime fish consumption from the SCS would pose little cancer and noncarcinogenic risk to coastal residents.

Quantitative evaluation of environmental risks of flotation tailings from hydrothermal sulfidation-flotation process.

Floatation tailings (FT) are the main by-products of the hydrothermal sulfidation-flotation process. FT (FT1 and FT2) were obtained by treating two different neutralization sludges (NS) (NS1 and NS2). This paper quantitatively evaluated the environmental risks of heavy metals (Zn, Cd, Cu, Pb, and As) in FT versus NS. The total concentration and leaching rates (R 2) of heavy metals in FT were much lower than those in NS, demonstrating that the hydrothermal sulfidation-flotation process was able to effectively suppress the mobility and leachability of heavy metals. The BCR-three sequence leaching procedure of FT confirmed that all metals were transformed into more stable forms (residue and oxidizable forms) than were found that in NS. The potential ecological risk index indicated that the overall risks caused by heavy metals decreased significantly from 6627.59 and 7229.67 (very serious risk) in NS1 and NS2, respectively, to 80.26 and 76.27 (low risk) in FT1 and FT2, respectively. According to the risk assessment code, none of the heavy metals in FT posed significant risk to the natural environment except Zn (with low risk). In general, the risk of heavy metals in FT had been well controlled.

Hydrothermal sulfidation and floatation treatment of heavy-metal-containing sludge for recovery and stabilization.

This study focuses on the application of hydrothermal sulfidation and floatation to treat the heavy-metal-containing sludge for recovery and stabilization. After the hydrothermal sulfidation, the sulfidation percentage of zinc and lead reach up to 85.0% and 75.4%, respectively. 33.3% of Zn, 58.9% of Pb and 68.8% of Cu can be recovered from the sludge by floatation. The lower recovery of ZnS attributes to its surface and structural characteristics. To compare these characteristics, three types of synthetic metal sulfide (ZnS, PbS and CuS) were prepared and examined with XRD, SEM and TEM. The poor floatability of the finely dispersed, round shape of ZnS can be improved by crystal modification in hydrothermal condition. With increasing the temperature and reaction time, the grain size of the ZnS increased from 7.95 nm to 44.28 nm and the recovery of Zn increased to from 33.3% to 72.8%. The TCLP results indicate that all the leached heavy metal concentrations of floatation tailings are under the allowable limit. No obvious increase of heavy metal concentration was observed in continuous leaching procedure. The presence of alkaline compounds after hydrothermal sulfidation might act as mineralogical scavengers of dissolved heavy metal released by sulfide oxidation to avoid the heavy metal pollution.