Preparation of deep eutectic solvent modified magnetic graphene oxide/metal organic framework nanocomposites for the extraction of three estrogens in cosmetics.

A novel magnetic dispersive solid phase extraction (MDSPE) procedure based on the deep eutectic solvent (DES) modified magnetic graphene oxide/metal organic frameworks nanocomposites (MGO@ZIF-8@DES) was established and used for the efficient enrichment of estradiol, estrone, and diethylstilbestrol in cosmetics (toner, lotion, and cream) for the first time. Then, the three estrogens were separated and determined by UHPLC-UV analysis method. In order to study the features and morphology of the synthesized adsorbents, various techniques such as FT-IR, SEM, and VSM measurements were executed. The MGO@ZIF-8@DES nanocomposites combine the advantages of high adsorption capacity, adequate stability in aqueous solution, and convenient separation from the sample solution. To achieve high extraction recoveries, the Box-Behnken design and single factor experiment were applied in the experimental design. Under the optimum conditions, the method detection limits for three estrogens were 20-30 ng g-1. This approach showed a good correlation coefficient (r more than 0.9998) and reasonable linearity in the range 70-10000 ng g-1. The relative standard deviations for intra-day and inter-day were beneath 7.5% and 8.9%, respectively. The developed MDSPE-UHPLC-UV method was successfully used to determine  three estrogens in cosmetics, and acceptable recoveries in the intervals of 83.5-95.9% were obtained. Finally, three estrogens were not detected in some cosmetic samples. In addition, the Complex GAPI tool was used to evaluate the greenness of the developed pretreatment method. The developed MDSPE-UHPLC-UV method is sensitive, accurate, rapid, and eco-friendly, which provides a promising strategy for determining hormones in different complex samples.

Interaction between laccase and diethylstilbestrol based on multispectral and chromatography analyses.

Diethylstilbestrol (DES) is a synthetic form of oestrogen that does not easily degrade in the environment and can be harmful to human health. Herein, the mechanism of the interaction between laccase and DES was investigated by various spectroscopic means and high-performance liquid chromatography (HPLC). The results of fluorescence experiments showed that the quenching of intrinsic fluorescence of laccase by DES was due to a static quenching, forming a binding site. According to the Förster non-radiative energy transfer theory (FRET), the action distance R0 between DES and laccase was 4.708 nm, r was 5.81 nm, and the energy transfer efficiency E was 22.08%, respectively. Both UV-Vis absorption spectra and FT-IR spectra indicated changes in the conformation and surroundings of the enzyme and changed in the secondary structure of laccase. Multispectral synthesis showed that the interaction of laccase with DES caused a change in the secondary structure of laccase. The degradation experiments showed that laccase could degrade DES, and the DES content decreased with time. This study provides a new theoretical basis and experimental method for further research on the reaction mechanism of the laccase degradation of DES. It may also provide a reference basis for human biological and environmental safety evaluations.

An ultrasensitive electrochemiluminescence aptasensor for the detection of diethylstilbestrol based on the enhancing mechanism of the metal-organic framework NH2-MIL-125(Ti) in a 3,4,9,10-perylenetetracarboxylic acid/K2S2O8 system.

In this work, a sensitive and selective electrochemiluminescent aptasensor was proposed based on the enhancing mechanism of the metal-organic framework NH2-MIL-125(Ti) in a 3,4,9,10-perylenetetracarboxylic acid/K2S2O8 system for a diethylstilbestrol assay. Herein, 3,4,9,10-perylenetetracarboxylic acid was selected as the major luminophore, and the metal-organic framework NH2-MIL-125(Ti) displayed a large specific surface area to immobilize abundant PTCA molecules to facilitate electrochemiluminescence efficiency. Besides, the metal-organic framework NH2-MIL-125(Ti) was used as a novel catalyst in the 3,4,9,10-perylenetetracarboxylic acid/K2S2O8 system, which could react with the co-reactant K2S2O8 to produce more SO4˙-. In addition, we introduced the amino-aptamer of diethylstilbestrol; due to the specific binding affinity between the aptamer and diethylstilbestrol, a selective electrochemiluminescent aptasensor for diethylstilbestrol was thus developed here. Under the optimal conditions, a wide detection range from 1.0 fM to 1.0 µM with a low detection limit of 0.28 fM (S/N = 3) was obtained. More importantly, the residual diethylstilbestrol in water was detected by the developed aptasensor; this confirmed that this method has good performance and potential applications in real samples.

Estrogen receptor alpha (ERα)-mediated coregulator binding and gene expression discriminates the toxic ERα agonist diethylstilbestrol (DES) from the endogenous ERα agonist 17ß-estradiol (E2).

Diethylstilbestrol (DES) is a synthetic estrogen and proven human teratogen and carcinogen reported to act via the estrogen receptor α (ERα). Since the endogenous ERα ligand 17ß-estradiol (E2) does not show these adverse effects to a similar extent, we hypothesized that DES' interaction with the ERα differs from that of E2. The current study aimed to investigate possible differences between DES and E2 using in vitro assays that detect ERα-mediated effects, including ERα-mediated reporter gene expression, ERα-mediated breast cancer cell (T47D) proliferation and ERα-coregulator interactions and gene expression in T47D cells. Results obtained indicate that DES and E2 activate ERα-mediated reporter gene transcription and T47D cell proliferation in a similar way. However, significant differences between DES- and E2-induced binding of the ERα to 15 coregulator motifs and in transcriptomic signatures obtained in the T47D cells were observed. It is concluded that differences observed in binding of the ERα with several co-repressor motifs, in downregulation of genes involved in histone deacetylation and DNA methylation and in upregulation of CYP26A1 and CYP26B1 contribute to the differential effects reported for DES and E2.

Multi-Residue Method for the Analysis of Stilbene Estrogens in Milk.

The rapid analysis of stilbene estrogens is crucially important in the environment, food and health sectors, but quantitation of lower detection limit for stilbene estrogens persists as a severe challenge. We herein described a homologous and sensitive fluorescence polarization (FP) assay based on estrogen receptor α ligand binding domain (ER-LBD) to monitor stilbene estrogens in milk. Under optimal conditions, the half maximal inhibitory concentrations (IC50) of the FP assay were 9.27 nM, 12.94 nM, and 22.38 nM for hexestrol, dienestrol and diethylstilbestrol, respectively. And the corresponding limits of detection (LOD) values were 2.94 nM, 2.89 nM, and 3.12 nM. Finally, the assay was applied to determine the stilbenes in milk samples where the mean recoveries ranged from 95.76% to 112.78% and the coefficients of variation (CV) below 12.00%. Furtherly, we have focused our study on high cross-reactivity phenomena by using two in silico approaches, including molecular docking analysis and topology analysis. Overall, docking results show that several residues in the hydrophobic pocket produce hydrophobic interactions with the tested drug molecules, which contribute to the stability of their binding. In this paper, we conclude that the FP method is suitable for the rapid detection of stilbenes in milk samples, requiring no expensive analytical equipment or time-consuming sample preparation. This work offers a practical approach that applies bioscience technology in food safety testing and improves analytical speed and laboratory efficiency.

Polyacetal-Based Combination Therapy for the Treatment of Prostate Cancer.

The high incidence of prostate carcinogenesis has prompted the search for novel effective treatment approaches. We have employed curcumin (Curc) and diethylstilbestrol (DES) to synthesize a series of polyacetal (PA)-based combination conjugates for prostate cancer (PCa) treatment. Given their bihydroxyl functionalities, Curc and DES molecules were incorporated into a PA mainchain using a one-pot reaction between diols and divinyl ethers. The PA-conjugates released both drugs under acidic conditions, such as those found in the tumor microenvironment, endosomes, or lysosomes, while remaining stable at neutral pH 7.4. The drug ratio was optimized to achieve anticancer drug synergism with elevated cytotoxicity against LNCaP-hormone-dependent human PCa cells conferred via the induction of S phase cell cycle arrest by the upregulation of p53 and CDK inhibitors p21Waf/CIP1 and downregulation of cyclin D1. The application of rationally designed PA-Curc-DES combination conjugates represents a potentially exciting new treatment for prostate cancer.

Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells.

In the present study, we investigated the activity and modes of action of cajanin stilbene acid (CSA) and its derivatives in terms of cytotoxicity, gene expression profile, and transcription factor activity. XTT assays on MCF7 cells were performed upon treatment with CSA or derivatives. After the determination of IC50 values, gene expression profiling was performed with Agilent microarray experiments. Deregulated genes were determined with Chipster software, pathway and functional analyses were performed with Ingenuity pathway software. In order to identify the potential upstream regulators, MatInspector software was used to perform transcription factor binding motif search in the promoter regions of the deregulated genes. Molecular docking on MYC/MAX complex and reporter cell line experiments were performed to validate the MYC inhibitory activity of CSA and its derivatives. Two known MYC inhibitors: 10058-F4 and 10074-G5 were used as positive control. All compounds showed cytotoxicities in the micromolar range. Microarray analyses pointed to cell cycle, DNA damage, and DNA repair as mainly affected cellular functions. Promoter motif analysis of the deregulated genes further supported the microarray gene expression analysis results emphasizing the relevance of transcription factors regulating cell cycle and proliferation, with MYC as being the most pronounced one. Luciferase-based reporter cell line experiments and molecular docking studies yielded supportive results emphasizing the inhibitory activity of CSA and its derivatives on MYC. CSA and its derivatives are shown to be promising anticancer compounds with low toxicity. They inhibit MYC activity comparable to 10058-F4 and 10074-G5. Further studies are warranted to analyze the therapeutic applicability of these compounds in more detail.

Prostaglandin D2 synthase related to estrogen in the female reproductive tract.

Prostaglandin D2 synthase (PTGDS), also known as a glutathione-independent prostaglandin D synthase, catalyzes prostaglandin H2 to prostaglandin D2 that exhibits functions that include regulation of the central nervous system, contraction/relaxation of smooth muscle and inhibition of platelet aggregation. Gene profiling data based on our previous study indicated that PTGDS is significantly increased during development, differentiation and remodeling of the oviduct in chickens in response to estrogen. Therefore, the aims of the present study were to investigate expression of PTGDS in the oviduct and examine if the relationship between PTGDS and estrogen is conserved during development and remodeling of the oviduct. Results of our study indicate d that PTGDS expression is specifically localized to the luminal (LE) and glandular epithelial (GE) cells of the chicken oviduct in response to diethylstilbestrol, a synthetic estrogen. In addition, PTGDS expression increased during the regeneration phase of the oviduct in concert with increasing concentrations of estrogen in the circulation of laying hens during induced molting. Moreover, PTGDS mRNA and protein were expressed abundantly in GE of ovarian carcinoma, but not in normal ovaries. These results provide the first evidence that PTGDS is a novel estrogen-stimulated gene in oviductal epithelial cells, as well as a candidate biomarker for diagnosis of ovarian carcinoma.

Pharmacokinetics and safety profiles of novel diethylstilbestrol orally dissolving film in comparison with diethylstilbestrol capsules in healthy Chinese male subjects.

OBJECTIVE: We compared the pharmacokinetic (PK) profiles of diethylstilbestrol orally dissolving film (DES ODF) and DES-capsule as well as assessing the safety, local tolerability, taste, and disintegration time of DES ODF. MATERIALS AND METHODS: Twelve healthy male volunteers receiving a single administration of 2.0 mg of DES ODF or DES-capsule were included in the study. The tolerability, taste, and time to dissolution of DES ODF were assessed after dosing. Safety assessments included adverse events, hematology and biochemistry tests, urinalysis, vital signs, and electrocardiography. RESULTS: The PK parameters of DES ODF were all greater than those of DEScapsule. The Cmax values were 5.64 ± 1.1 and 3.4 ± 1.93 ng/mL for DES ODF and DES-capsule, respectively. Assessment of bioequivalence was based on the 90% CIs of the treatment ratios of the log-transformed Cmax, AUC0-t, and AUC0-∞ (DES ODF to DES-capsule), with the mean values being 1.93 (141 - 264), 1.24 (98 - 156), and 1.59 (121 - 207), respectively, indicating that DES ODF had a significantly high bioavailability. The mean DES ODF disintegration time was 14 ± 5 minutes. DES ODF was well tolerated and no serious adverse events or clinically relevant changes were observed. CONCLUSIONS: The DES ODF is well tolerated and better absorbed in comparison with DES-capsule.

Structural insights into Resveratrol's antagonist and partial agonist actions on estrogen receptor alpha.

BACKGROUND: Resveratrol, a naturally occurring stilbene, has been categorized as a phytoestrogen due to its ability to compete with natural estrogens for binding to estrogen receptor alpha (ERα) and modulate the biological responses exerted by the receptor. Biological effects of resveratrol (RES) on estrogen receptor alpha (ERα) remain highly controversial, since both estrogenic and anti-estrogenic properties were observed. RESULTS: Here, we provide insight into the structural basis of the agonist/antagonist effects of RES on ERα ligand binding domain (LBD). Using atomistic simulation, we found that RES bound ERα monomer in antagonist conformation, where Helix 12 moves away from the ligand pocket and orients into the co-activator binding groove of LBD, is more stable than RES bound ERα in agonist conformation, where Helix 12 lays over the ligand binding pocket. Upon dimerization, the agonistic conformation of RES-ERα dimer becomes more stable compared to the corresponding monomer but still remains less stable compared to the corresponding dimer in antagonist conformation. Interestingly, while the binding pocket and the binding contacts of RES to ERα are similar to those of pure agonist diethylstilbestrol (DES), the binding energy is much less and the hydrogen bonding contacts also differ providing clues for the partial agonistic character of RES on ERα. CONCLUSIONS: Our Molecular Dynamics simulation of RES-ERα structures with agonist and antagonist orientations of Helix 12 suggests RES action is more similar to Selective Estrogen Receptor Modulator (SERM) opening up the importance of cellular environment and active roles of co-regulator proteins in a given system. Our study reveals that potential co-activators must compete with the Helix 12 and displace it away from the activator binding groove to enhance the agonistic activity.

Graphene oxide-modified electrodes for sensitive determination of diethylstilbestrol.

This paper reports an electrochemical sensor fabricated with graphene oxide (GO) modified on a chitosan-coated glassy carbon electrode (GO-CS/GCE) and its application for the detection of diethylstilbestrol (DES). It was observed that the effective electrochemical surface area of the GO modified electrode was nearly 10 times that of the bare GCE. This could be used to explain the results that the oxidation peak current of DES on the GO-CS/GCE was much larger than on the bare GCE. Under optimized conditions, the prepared electrode could be used to electrochemically detect DES according to the oxidation of the DES. Based on the technique of differential pulse voltammetry and the accumulation of DES on GO modified electrodes, the calibration curve for DES determination could be obtained with a linear range of 1.5 × 10(-8)-3.0 × 10(-5) M and an estimated detection limit of 3.0 × 10(-9) M (S/N = 3). The feasibility of the developed electrode for tablet sample analysis was investigated. Our investigation revealed that GO could significantly improve the analytical performance of electrochemical sensors.

Identification of physiologically active substances as novel ligands for MRGPRD.

Mas-related G-protein coupled receptor member D (MRGPRD) is a G protein-coupled receptor (GPCR) which belongs to the Mas-related GPCRs expressed in the dorsal root ganglia (DRG). In this study, we investigated two novel ligands in addition to beta-alanine: (1) beta-aminoisobutyric acid, a physiologically active substance, with which possible relation to tumors has been seen together with beta-alanine; (2) diethylstilbestrol, a synthetic estrogen hormone. In addition to the novel ligands, we found that transfection of MRGPRD leads fibroblast cells to form spheroids, which would be related to oncogenicity. To understand the MRGPRD novel character, oncogenicity, a large chemical library was screened in order to obtain MRGPRD antagonists to utilize in exploring the character. The antagonist in turn inhibited the spheroid proliferation that is dependent on MRGPRD signaling as well as MRGPRD signals activated by beta-alanine. The antagonist, a small-molecule compound we found in this study, is a potential anticancer agent.

Sorption of estrogens estrone, 17ß-estradiol, estriol, 17α-ethinylestradiol, and diethylstilbestrol on sediment affected by different origins.

The sorption coefficients of estrone (E1), 17ß-estradiol (E2), and estriol (E3), 17α-ethinylestradiol (EE2), and diethylstilbestrol (DES) on four sediments (BS1-4) collected downstream of agricultural, domestic, and industrial discharges were determined. The objective was to investigate the effect of sediment origin on the sorption affinity of natural and synthetic estrogens on sediments. Experimental results indicate that the sediment samples from different origins had differing estrogen sorption affinities. Organic materials in sediment samples collected from downstream of agricultural and domestic discharge, i.e., BS1 and BS2, respectively, were readily biodegraded and biotransformed during sediment diagenesis, which enhanced the sorption capacity for estrogens. Sediment samples BS3 and BS4, which were obtained downstream of domestic and industrial discharges, respectively, may contain complex compositions, including hydrophilic substances that resulted in lower log K(oc) values. The estrogen sorption on sediments was reasonably regressive with linear models. The log K(oc) values for individual estrogens in individual sediments showed variation: 2.82-4.21 for E1; 2.73-4.14 for E2; 2.19-3.76 for E3; 3.24-3.94 for EE2; and, 4.07-5.25 for DES. Nevertheless, the relationship between log K(ow) and log K(oc) of individual estrogens in individual sediments was linear. The mean log K(oc) values for target estrogens followed the trend of DES (4.68) > EE2 (3.71) > E2 (3.52) > E1 (3.44) > E3 (2.99), corresponding to the trend of log K(ow) values. These analytical results suggest that sorption of estrogens on sediments varied with sample origin. Therefore, evaluations of the fate and transport of estrogens in river environments must consider surrounding agricultural, domestic, and industrial sources.

Estrogenic compounds and estrogenicity in surface water, sediments, and organisms from Yundang Lagoon in Xiamen, China.

Seven estrogenic compounds--estrone (E1), 17ß-estradiol (E2), 17α-ethynylestradiol (EE2), diethylstilbestrol (DES), nonylphenol (NP), octylphenol (OP), and bisphenol A (BPA)--in sediments, surface water, pore water, and organisms were investigated and estrogenic activities were estimated by examining estradiol equivalent (EEQ) concentrations in Yundang Lagoon of Xiamen. The results showed that estrogenic compounds were present in all matrixes of interest: in surface water, ranging from 609.61 to 711.31 ng/l; in pore water, ranging from 562.12 to 1038.15 ng/l; in sediments, ranging from 1433.12 to 2060.41 ng/g; and in biota samples, ranging from 1373.76 to 3199.09 ng/g (lipid weight). NP was the predominant component in all collected samples and the highest concentration was 1964.80 ng/g in sediment. Total EEQ ranged from 4.56 to 13.79 ng/l in surface water, from 2.40 to 17.16 ng/l in pore water, and from 8.66 to 23.95 ng/g in sediments. However, major contributors to total EEQ concentrations were E2, E1, and DES. The EEQ concentrations in surface water samples were at a higher level in comparison to that reported in European countries. To biological sample, the highest level of total estrogenic compounds was found in the short-necked clam. Higher values of the biota-sediment accumulation factor (BSAF) were found in short-necked clam and black seabream, indicating that the living habits of organism and physical-chemical properties of estrogenic compounds might influence the bioavailability of estrogenic compounds in organisms.

Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains.

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.

The cajanine derivative LJ101019C regulates the proliferation and enhances the activity of NK cells via Kv1.3 channel-driven activation of the AKT/mTOR pathway.

BACKGROUND: Natural killer (NK) cells play important roles in immune responses and have been wildly used in immunotherapy. Nevertheless, some limitations remain. It is urgent to explore novel and safe strategies to enhance NK cell activity. PURPOSE: The aim of this study was to investigate the immuno-stimulatory effects and to reveal the molecular mechanism of LJ101019C, a derivative of a natural small-molecule compounds cajanine, on NK cells. METHODS: Cell proliferation was examined by CCK8 assay, then we used the cytotoxicity detection kit to detect the cytotoxicity of NK cells. The change of cell cycle, intracellular reactive oxygen species (ROS) level and mitochondrial mass were evaluated by FACS and Operetta high-content image analysis, respectively. Furthermore, the IFN-γ secretion of NK cells were measured by ELISA. The Kv1.3 protein expression and function were detected by western blot and patch-clamp technique, respectively. The role of Kv1.3 in AKT/mTOR pathway activation was determined by western blot. RESULTS: The results showed that LJ101019C at relatively low concentrations (0.05-0.1 µM) significantly increased the proliferation of NK cells. And 1 µM LJ101019C could elevate the proportion of NK cells in the S-phase of the cell cycle (*p < 0.1). Furthermore, the cytotoxic effects of NK cells targeting MIA PaCa-2 cells were significantly enhanced by 0.1 and 1 µM LJ101019C, and were associated with the enhanced secretion of IFN-γ by NK cells (*p < 0.1; **p < 0.05). 0.1 and 1 µM LJ101019C increased intracellular levels of ROS (**p < 0.05), and 0.1 µM LJ101019C elevated mitochondrial mass (*p < 0.1). Electrophysiological recordings indicated that LJ101019C led to a remarkably increase the Kv1.3 current density. Moreover, western blot results indicated that LJ101019C elevated Kv1.3 protein expression and activated AKT/mTOR signaling via increasing the expression of Kv1.3 in NK cells. CONCLUSION: LJ101019C increases the proliferation and the cytotoxicity of NK cells at relatively low concentrations. The mechanism is the activation of AKT/mTOR signaling pathway driven by up-regulation of Kv1.3 in NK cells. These suggest LJ101019C is a promising candidate for improving the efficacy of NK cell-based immunotherapies.

Mechanism of metabolic activation and DNA adduct formation by the human carcinogen diethylstilbestrol: the defining link to natural estrogens.

Diethylstilbestrol (DES) is a human carcinogen, based on sufficient epidemiological evidence. DES is mainly metabolized to its catechol, 3'-hydroxyDES (3'-OH-DES), which can further oxidize to DES-3',4'-quinone (DES-3',4'-Q). Similarly to estradiol-3,4-quinone, the reaction of DES-3',4'-Q with DNA would form the depurinating 3'-OH-DES-6'-N3Ade and 3'-OH-DES-6'-N7Gua adducts. To prove this hypothesis, synthesis of DES-3',4'-Q by oxidation of 3'-OH-DES with Ag(2)O was tried; this failed due to instantaneous formation of a spiro-quinone. Oxidation of 3'-OH-DES by lactoperoxidase or tyrosinase in the presence of DNA led to the formation of 3'-OH-DES-6'-N3Ade and 3'-OH-DES-6'-N7Gua adducts. These adducts were tentatively identified by LC-MS/MS as 3'-OH-DES-6'-N3Ade, m/z = 418 [M+H](+), and 3'-OH-DES-6'-N7Gua, m/z = 434 [M+H](+). Demonstration of their structures derived from their oxidation by MnO(2) to the DES quinone adducts and subsequent tautomerization to the dienestrol (DIES) catechol adducts, which are identical to the standard 3'-OH-DIES-6'-N3Ade, m/z = 416 [M+H](+), and 3'-OH-DIES-6'-N7Gua, m/z = 432 [M+H](+), adducts. The reaction of DIES-3',4'-Q or lactoperoxidase-activated 3'-OH-DIES with DNA did not produce any depurinating adducts, due to the dienic chain being perpendicular to the phenyl planes, which impedes the intercalation of DIES into the DNA. Enzymic oxidation of 3'-OH-DES suggests that the catechol of DES intercalates into DNA and is then oxidized to its quinone to yield N3Ade and N7Gua adducts. These results suggest that the common denominator of tumor initiation by the synthetic estrogen DES and the natural estrogen estradiol is formation of their catechol quinones, which react with DNA to afford the depurinating N3Ade and N7Gua adducts.

Sonophotocatalysis of endocrine-disrupting chemicals.

Sonolysis and photolysis often exhibit synergistic effects in the degradation of organic molecules. An assay of fish oocyte maturation provides an appropriate experimental system to investigate the hormonal activities of chemical agents. Oocyte maturation in fish is triggered by maturation-inducing hormone (MIH), which acts on receptors on the oocyte surface. A synthetic estrogen, diethylstilbestrol (DES), possesses inducing activity of fish oocyte maturation, and a widely used biocide, pentachlorophenol (PCP), exhibits a potent inhibitory effect on fish oocyte maturation. In this study, the effects of the combined treatment by sonolysis with photolysis (sonophotocatalysis) to diminish the hormonal activity of DES and the maturation preventing activity of PCP was examined. By sonophotocatalysis, hormonal activity of DES was completely lost within 30 min and the inhibiting activity of PCP was lost within 120 min. These results demonstrated that sonophotocatalysis is effective for diminishing the endocrine-disrupting activity of chemical agents.

Persulfate-assisted photodegradation of diethylstilbestrol using monoclinic BiVO4 under visible-light irradiation.

In this study, the photosynergistic performance of BiVO4 with persulfate (PS) is demonstrated under visible light irradiation for the first time. Diethylstilbestrol (DES) was selected as a reluctant compound, and factors including dosages of PS and catalyst, solution pHs, initial concertration of DES, and inorganic anions were evaluated. The morphology and chemical state of bismuth vanadate (BiVO4) was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectrometer (EDS), and ultraviolet-visible (UV-Vis) diffuse reflectance spectroscopy (DRS). It was found that the degradation of DES was promoted in either acid or alkaline solutions. The increase of PS and BiVO4 dosages was beneficial to the reactions, while incremental concentration of DES showed the inhibiting effect. By scavenging hVB+, Cl- was able to make the promotion, differentiated from the exsiting HCO- 3. Moreover, the photocatalytic mechanism for the BiVO4/PS/vis-light system was proposed by using several probe compounds (isopropanol, tert-butanol, and 1,4-benzoquinone), which consists of h+ VB/e- CB generation and recombination on the surface of BiVO4 as well as free radical oxidation in the solutions. The study provides a distinctive method to treat organic contaminants using visible light in the aqueous environment.

UV photoconversion of environmental oestrogen diethylstilbestrol and its persistence in surface water under sunlight.

As one of the most oestrogenic synthetic compounds in water environment, diethylstilbestrol (DES) has been studied for decades. Some studies showed that DES can be removed by ultraviolet (UV) irradiation. However, no one has paid attention to the formation of oestrogenic disinfection by-products (DBPs) and the persistence of DES in surface water remains a mystery. In this study, UV was found to be very effective in removing oestrogenic activity regardless of water quality. Three oestrogenic DBPs were specifically isolated by oestrogen receptor-based affinity chromatography and identified as 9,10-diethylphenanthrene-3,6-diol, cis-DES and Z,Z-dienestrol. Among them, 9,10-diethylphenanthrene-3,6-diol was proved to have stronger oestrogenic activity than E2, but it can be further photodegraded. In addition, DES was also demonstrated to be a photochromic compound, whose UV-induced intermediates can be transformed back to DES under sunlight, which significantly slows down the photodegradation of DES. This study solves the question as to why UV-degradable DES is still detectable in the ambient water and provides a deep understanding of DES removal during UV disinfection.