Environmental risk assessment of selected organic chemicals based on TOC test and QSAR estimation models.

Environmental risks of organic chemicals have been greatly determined by their persistence, bioaccumulation, and toxicity (PBT) and physicochemical properties. Major regulations in different countries and regions identify chemicals according to their bioconcentration factor (BCF) and octanol-water partition coefficient (Kow), which frequently displays a substantial correlation with the sediment sorption coefficient (Koc). Half-life or degradability is crucial for the persistence evaluation of chemicals. Quantitative structure activity relationship (QSAR) estimation models are indispensable for predicting environmental fate and health effects in the absence of field- or laboratory-based data. In this study, 39 chemicals of high concern were chosen for half-life testing based on total organic carbon (TOC) degradation, and two widely accepted and highly used QSAR estimation models (i.e., EPI Suite and PBT Profiler) were adopted for environmental risk evaluation. The experimental results and estimated data, as well as the two model-based results were compared, based on the water solubility, Kow, Koc, BCF and half-life. Environmental risk assessment of the selected compounds was achieved by combining experimental data and estimation models. It was concluded that both EPI Suite and PBT Profiler were fairly accurate in measuring the physicochemical properties and degradation half-lives for water, soil, and sediment. However, the half-lives between the experimental and the estimated results were still not absolutely consistent. This suggests deficiencies of the prediction models in some ways, and the necessity to combine the experimental data and predicted results for the evaluation of environmental fate and risks of pollutants.

Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions.

Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure-activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model. Dioxin-like CB126, but not non-dioxin-like CB153, significantly enhanced 17ß-estradiol (E2) biosynthesis in a dose-dependent manner. Among the genes related to estrogen metabolism, the level of 17ß-hydroxysteroid dehydrogenase 7 (HSD17B7) showed significant increase following CB126 exposure. We further found that CB126 exposure decreased the methylation of the HSD17B7 promoter. Elevated expression of HSD17B7 was observed in the eutopic endometrium of EM patients. CB126 rather than CB153 triggered the inflammatory response by directly stimulating the secretion of inflammatory factors and indirectly reducing the level of lipoxin A4 (LXA4). Furthermore, the inflammation enhanced the expression of HSD17B7. Antagonism of the aryl hydrocarbon receptor (AhR) diminished the effects induced by CB126. In vivo, the PCB-treated EM mouse model confirmed that CB126 rather than CB153 increased the levels of both E2 and inflammatory factors in peritoneal fluid and promoted the development of endometriotic lesions. In all, CB126, but not CB153, triggered EM development by stimulating estrogen biosynthesis, inflammation and their interactions and that these effects were mediated by the AhR receptor.

In situ combined chemical and biological assessment of estrogenic pollution in a water recycling system.

Estrogenic pollution and its control in aquatic systems have drawn substantial attention around the world. The chemical and biological assessment approaches currently utilized in the laboratory or field cannot give an integrated assessment of the pollution when used separately. In this study, in situ chemical and biological methods were combined to detect pollution in a water recycling system. Data for the water quality index (WQI) demonstrated that the water treatment resulted in the decline of pollution from upstream to downstream. Wild male Nile tilapia, Oreochromis niloticus, was sampled in June and September. The concentrations of four common endocrine disrupting chemicals (EDCs) were determined in the tilapia liver by chromatographic analysis methods. The level of 17ß-estradiol (E2) declined from upstream to downstream in both months. In contrast, the levels of bisphenol A (BPA), di-(2-ethylhcxyl) phthalate (DEHP), and perfluorooctane sulfonate (PFOS) did not display this declining tendency. The highest relative expression of vitellogenin 1 (VTG1) was observed in tilapia from upstream, then the level significantly decreased along the water system. The relative expression levels of CYP1A1 in the water system were also significantly higher than that of the control. However, no declining trend could be observed along the water system. The change of VTG1 expression corresponded well with that of E2 levels in the tilapia liver. Overall, our study assessed the pollution by endocrine disruptors using chemical and biological data with good correspondence. This study also demonstrated the effectiveness of the water recycling system in eliminating estrogen pollution in municipal sewage.

Immunotoxic effects of perfluorooctane sulfonate and di(2-ethylhexyl) phthalate on the marine fish Oryzias melastigma.

Perfluorooctane sulfonate (PFOS) and di(2-ethylhexyl) phthalate (DEHP) have both been reported to induce adverse effects including immunotoxicity. Despite the widespread presence of these two chemicals in estuaries and seawater, their health effects on marine fish have received little attention. Oryzias melastigma is a potential marine fish model for immunological studies. In the present study, immune-related genes in O. melastigma were enriched at the transcriptome level. Three-month-old fish were exposed to PFOS and DEHP (single or combined) for one week. The liver index-hepatosomatic index (HSI) of the fish was higher in the PFOS-exposed group and combined group than in the control group. This result indicates that PFOS might lead to liver toxicity. The mRNA level of interleukin-1 beta (IL1ß) was upregulated after exposure. For catalase (CAT), glutathione peroxidase (GPx) and cluster of differentiation 3 (CD3), single exposure did not affect mRNA levels, but the combined exposure did significantly alter the expression of these genes. In all, our study provides a useful reference for immunotoxicological studies with O. melastigma; it also highlights the importance of assessing the combined effects of pollutant mixtures when determining the risk to aquatic organisms.

RMI1 facilitates repair of ionizing radiation-induced DNA damage and maintenance of genomic stability.

Ionizing radiation (IR) causes a wide variety of DNA lesions, of which DNA double-stranded breaks (DSBs) are the most deleterious. Homologous recombination (HR) is a crucial route responsible for repairing DSBs. RecQ-mediated genome instability protein 1 (RMI1) is a member of an evolutionarily conserved Bloom syndrome complex, which prevents and resolves aberrant recombination products during HR, thereby promoting genome stability. However, little is known about the role of RMI1 in regulating the cellular response to IR. This study aimed to understand the cellular functions and molecular mechanisms by which RMI1 maintains genomic stability after IR exposure. Here, we showed IR upregulated the RMI1 protein level and induced RMI1 relocation to the DNA damage sites. We also demonstrated that the loss of RMI1 in cells resulted in enhanced levels of DNA damage, sustained cell cycle arrest, and impaired HR repair after IR, leading to reduced cell viability and elevated genome instability. Taken together, our results highlighted the direct roles of RMI1 in response to DNA damage induced by IR and implied that RMI1 might be a new genome safeguard molecule to radiation-induced damage.

The Inflammation Response to DEHP through PPARγ in Endometrial Cells.

Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s) behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa) were recruited to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT) as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

The inflammation and estrogen metabolism impacts of polychlorinated biphenyls on endometrial cancer cells.

Polychlorinated biphenyls (PCBs) are persistent and bio-accumulative chemicals that provoke a wide range of toxic effects. Their adverse impacts on the reproductive system are of great concern, however, the effects of PCBs on endometrium are still unclear. In the study, the endometrial adenocarcinoma Ishikawa cells were exposed to both dioxin-like CB126 and non-dioxin-like CB153 at the nominal concentrations of 0.3, 3, and 30µM. The inflammatory and endocrine effects were detected after treatment by PCBs. Results showed that CB126 stimulated the proliferation of Ishikawa cells at lower concentrations of 0.3 and 3µM. By contrast, CB153 did not affect the viability of the cells. Both congeners exerted the stimulatory effects on the enzymatic activity of SOD1. CB126 decreased the abundance of Interleukin-8 both at the mRNA and protein levels. Blocking of estrogen receptor or aryl hydrocarbon receptor by the antagonist abolished the effects of CB126 on the expressions of inflammatory factors. The levels of testosterone and 17beta-estradiol were not changed after exposure to lower doses of PCBs. In accordance, PCBs did not affect the mRNA expressions of estrogen metabolism-related genes. In all, our study revealed that PCBs affected the expression of inflammatory factors through ER and AHR receptors, however, no toxic effects were observed on estrogen metabolism.