DDX20 positively regulates the interferon pathway to inhibit viral infection.

The DEAD-box (DDX) family comprises RNA helicases characterized by the conserved sequence D(Asp)-E(Glu)-A(Ala)-D(Asp), participating in various RNA metabolism processes. Some DDX family members have been identified for their crucial roles in viral infections. In this study, RNAi library screening of the DDX family unveiled the antiviral activity of DDX20. Knockdown of DDX20 enhanced the replication of viruses such as vesicular stomatitis virus (VSV) and herpes simplex virus type I (HSV-1), while overexpression of DDX20 significantly diminished the replication level of these viruses. Mechanistically, DDX20 elevated the phosphorylation level of IRF3 induced by external stimuli by facilitating the interaction between TBK1 and IRF3, thereby promoting the expression of IFN-ß. The increased IFN-ß production, in turn, upregulated the expression of interferon-stimulated genes (ISGs), including Cig5 and IFIT1, thereby exerting the antiviral effect. Finally, in an in vivo infection study, Ddx20 gene-deficient mice exhibited increased susceptibility to viral infection. This study provides new evidence that DDX20 positively modulates the interferon pathway and restricts viral infection.

[Exposure characteristics and health risk assessment of 97 typical chemical pollutants in human serum].

Rapid industrial and agricultural developments in China have led to the wide use and discharge of chemical products and pesticides, resulting in extensive residues in environmental media. These residues can enter the human body through various pathways, leading to high exposure risks and health hazards. Because the human body is exposed to a variety of chemical pollutants, accurately quantifying the exposure levels of these pollutants in the human body and evaluating their health risks are of great importance. In this study, the serum concentrations of 97 typical chemical pollutants of 60 adults in central China were simultaneously determined using solid-phase extraction coupled with gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS). In this method, 200 µL of a serum sample was mixed with 10 µL of an isotope-labeled internal standard solution. The sample was vortexed and refrigerated overnight at 4 ℃. Each sample was then deproteinized by the addition of 200 µL of 15% formic acid aqueous solution and vortexed. The serum sample was loaded into a preconditioned Oasis® PRiME HLB SPE cartridge and rinsed with 3 mL of methanol-water (6∶1, v/v). The SPE cartridge was subsequently vacuumed. The analytes were eluted with 3 mL of dichloromethane followed by 3 mL of n-hexane. The eluent was concentrated to near dryness under a gentle nitrogen stream and reconstituted with 100 µL of acetone. The samples were determined by GC-MS/MS and separated on a DB-5MS capillary column (30 m×0.25 mm×0.25 µm) with temperature programming. The column temperature was maintained at 70 ℃ for 2 min, increased at a rate of 25 ℃/min to 150 ℃, increased at a rate of 3 ℃/min to 200 ℃, and then held for 2 min. Finally, the column temperature was increased at a rate of 8 ℃/min to 300 ℃ and maintained at this temperature for 8 min. The samples were detected in multiple-reaction monitoring (MRM) mode and quantitatively analyzed using the internal standard method. Multiple linear regression models were used to analyze the effects of demographic characteristics, lifestyle habits, and diet on the concentrations of the chemical pollutants in the serum samples, and known biomonitoring equivalents (BEs) and human biomonitoring (HBM) values were combined to compute hazard quotients (HQs) and hazard indices (HIs) and evaluate the health risks of single and cumulative exposures to the chemical pollutants. The results showed that the main pollutants detected in human serum were organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The detection rates of eight pollutants, including hexachlorobenzene (HCB) (100%), pentachlorophenol (PCP) (100%), p,p'-dichlorodiphenylene (p,p'-DDE) (100%), PCB-138 (100%), PCB-153 (98.3%), ß-hexachlorocyclohexane (ß-HCH) (91.7%), fluorene (Flu) (85.0%), and anthracene (Ant) (75.0%), were greater than 70%. The serum levels of ß-HCH were higher in females than in males, and age was positively correlated with exposure to p,p'-DDE, PCB-138, PCB-153, and ß-HCH. Increased exposure levels to p,p'-DDE and ß-HCH may be associated with a high frequency of meat intake, whereas increased exposure level to PCP may be associated with a high frequency of vegetable intake. The serum HQ of PCP was greater than 1 in 6.7% of the samples, and no risk was observed for HCB and p,p'-DDE exposure in the study population. Approximately 28.3% of the study subjects had HI values greater than 1. Overall, the general adult population in this region is widely exposed to a wide range of chemical pollutants, and gender, age, and diet are likely to be the main factors influencing the concentration of chemical pollutants. The health risk of single and compound exposures to chemical pollutants should not be ignored.

DNA methylation reprogramming mediates transgenerational diabetogenic effect induced by early-life p,p'-DDE exposure.

Increasing evidence shows that an adverse environment during the early fetal development can affect the epigenetic modifications on a wide range of diabetes-related genes, leading to an increased diabetic susceptibility in adulthood or even in subsequent generations. p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is a break-down product of the pesticide dichlorodiphenyltrichloroethane (DDT). p,p'-DDE has been associated with various health concerns, such as diabetogenic effect. However, the precise molecular mechanism remains unclear. In this study, p,p'-DDE was given by gavage to pregnant rat dams from gestational day (GD) 8 to GD15 to generate male germline to investiagate the transgenerational effects. We found that early-life p,p'-DDE exposure increased the transgenerational diabetic susceptibility through male germline inheritance. In utero exposure to p,p'-DDE altered the sperm DNA methylome in F1 progeny, and a significant number of those differentially methylated genes could be inherited by F2 progeny. Furthermore, early-life p,p'-DDE exposure altered DNA methylation in glucose metabolic genes Gck and G6pc in sperm and the methylation modification were also found in liver of the next generation. Our study demonstrate that DNA methylation plays a critical role in mediating transgenerational diabetogenic effect induced by early-life p,p'-DDE exposure.

Assessment of endocrine disruptor impacts on lipid metabolism in a fatty acid-supplemented HepaRG human hepatic cell line.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental contaminants is one of the risk factors and an increasing amount of evidence points to a role for endocrine disrupting compounds (EDCs). This study assesses the impact of selected EDCs on the formation of lipid droplets, the marker for steatosis in a hepatic model. The mechanisms underlying this effect are then explored. Ten compounds were selected according to their obesogenic properties: bisphenol A, F and S, butyl-paraben, cadmium chloride, p,p'-DDE, DBP, DEHP, PFOA and PFOS. Using a 2D or 3D model, HepaRG cells were exposed to the compounds with or without fatty acid supplementation. Then, the formation of lipid droplets was quantified by an automated fluorescence-based method. The expression of genes and proteins involved in lipid metabolism and the impact on cellular respiration was analyzed. The formation of lipid droplets, which is revealed or enhanced by oleic acid supplementation, was most effectively induced by p,p'-DDE and DEHP. Experiments employing either 2D or 3D culture conditions gave similar results. Both compounds induced the expression of PLIN2. p,p'-DDE also appears to act by decreasing in fatty acid oxidation. Some EDCs were able to induce the formation of lipid droplets, in HepaRG cells, an effect which was increased after supplementation of the cells with oleic acid. A full understanding of the mechanisms of these effects will require further investigation. The novel automated detection method described here may also be useful in the future as a regulatory test for EDC risk assessment.

The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice.

DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NO•- production and IL-1ß secretion, but increasing cellular ROS and mitochondrial O2•-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-ß1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NO•- production by the p,p'-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O2 suggests that p,p'-DDE interferes with the iNOS function but not with its transcription. The p,p'-DDE decreasing of IL-1ß secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1ß secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1ß secretion process, as the NLRP3 activation, deserves further study.

Efficient in vivo and in silico assessments of antiandrogenic potential in zebrafish.

This study aimed to establish zebrafish-based in vivo and in silico assay systems to evaluate the antiandrogenic potential of environmental chemicals. Zebrafish embryos were exposed to 17α-methyltestosterone (TES) alone or coexposed to TES and representative antiandrogens including flutamide, p,p'-DDE, vinclozolin, fenitrothion, and linuron. We assessed the transcript expression of the androgen-responsive gene sulfotransferase family 2, cytosolic sulfotransferase 3 (sult2st3). The expression of sult2st3 was significantly induced by TES in the later stages of embryonic development. However, the TES-induced expression of sult2st3 was inhibited by flutamide in a concentration-dependent manner (IC50: 5.7 µM), suggesting that the androgen receptor (AR) plays a role in sult2st3 induction. Similarly, p,p'-DDE, vinclozolin, and linuron repressed the TES-induced expression of sult2st3 (IC50s: 0.35, 3.9, and 52 µM, respectively). At the highest concentration tested (100 µM), fenitrothion also suppressed sult2st3 expression almost completely. Notably, p,p'-DDE and linuron did not inhibit sult2st3 induction due to higher concentrations of TES; instead, they potentiated TES-induced sult2st3 expression. Fenitrothion and linuron, which had relatively low antiandrogenic potentials in terms of sult2st3 inhibition, induced broader toxicities in zebrafish embryos; thus, the relationship between developmental toxicities and antiandrogenic potency was unclear. Additionally, an in silico docking simulation showed that all five chemicals interact with the zebrafish AR at relatively low interaction energies and with Arg702 as a key amino acid in ligand binding. Our findings suggest that a combination of zebrafish-based in vivo and in silico assessments represents a promising tool to assess the antiandrogenic potentials of environmental chemicals.

Dietary exposure to environmentally relevant pesticide mixtures impairs swimming performance and lipid homeostatic gene expression in Juvenile Chinook salmon at elevated water temperatures.

Aquatic organisms are exposed to complex mixtures of pesticides in the environment, but traditional risk assessment approaches typically only consider individual compounds. In conjunction with exposure to pesticide mixtures, global climate change is anticipated to alter thermal regimes of waterways, leading to potential co-exposure of biota to elevated temperatures and contaminants. Furthermore, most studies utilize aqueous exposures, whereas the dietary route of exposure may be more important for fish owing to the hydrophobicity of many pesticides. Consequently, the current study aimed to determine the effects of elevated temperatures and dietary pesticide mixtures on swimming performance and lipid metabolism of juvenile Chinook salmon, Oncorhynchus tshawytscha. Fish were fed pesticide-dosed pellets at three concentrations and three temperatures (11, 14 and 17 °C) for 14 days and swimming performance (Umax) and expression of genes involved in lipid metabolism and energetics were assessed (ATP citrate lyase, fatty acid synthase, farnesoid x receptor and liver x receptor). The low-pesticide pellet treatment contained five pesticides, p,p'-DDE, bifenthrin, esfenvalerate, chlorpyrifos and fipronil at concentrations based on prey items collected from the Sacramento River (CA, USA) watershed, with the high-pesticide pellet treatment containing a six times higher dose. Temperature exacerbated effects of pesticide exposure on swimming performance, with significant reductions in Umax of 31 and 23% in the low and high-pesticide pellet groups relative to controls at 17 °C, but no significant differences in Umax among pesticide concentrations at 11 or 14 °C. At 14 °C there was a significant positive relationship between juvenile Chinook salmon pesticide body residues and expression of ATP citrate lyase and fatty acid synthase, but an inverse relationship and significant downregulation at 17 °C. These findings suggest that temperature may modulate effects of environmentally relevant pesticide exposure on salmon, and that pesticide-induced impairment of swimming performance may be exacerbated under future climate scenarios.

Metallothionein gene expression in rat tissues: response to dietary restriction after orally dichlorodiphenyldichloroethylene (DDE) exposure and high-fat feeding.

Dichlorodiphenyldichloroethylene (DDE) is an environmental pollutant that accumulates in adipose tissue through the food chain. Hypercaloric, high-fat diet is considered to promote the accumulation of toxic lipophilic substances in tissues, whereas the loss of body fat through caloric restriction results in a recirculation of these substances. In rats, oral administration of DDE causes the onset of tissues damage; the concomitant intake of a high-fat diet ameliorates tissues status, probably because of the entrapment of the lipophilic substance in fat depots. Recent evidence demonstrates that DDE alters the expression of metallothioneins, proteins involved in cellular defense from oxidative stress, in a diet- and tissue-specific manner. This study is aimed to verify if 2 weeks of caloric restriction after the oral DDE treatment can modify metallothionein gene expression in tissues of high-fat fed rats. Real-time PCR analysis demonstrates that metallothionein gene expression after calorie restriction is tissue-specific and strongly influenced by both previous dietary conditions and DDE exposure. To avoid misleading conclusions on the interference of toxic xenobiotics on metallothionein gene expression is particularly important to consider the tissue, the cellular conditions, and the nutritional status of the animals, especially when the protein is used as an index of cells health.

Organochlorine pesticides induce epithelial as well as inflammatory mediators following exposure to human ovarian surface epithelial cells: An in vitro study.

Although studies have suggested organochlorine pesticides (OCPs) exposure increased the risk of epithelial ovarian cancer, the mechanisms underlying its potential tumorigenic effects in the human ovary are not well understood. In this study, we investigated the impact of dichlorodiphenyldichloroethylene (DDE), endosulfan, and heptachlor exposure on epithelial cadherin (E-cadherin) and proinflammatory mediators in human ovary surface epithelial (HOSE) cells. We found that DDE, endosulfan, and heptachlor exposure resulted in epithelial differentiation accompanied by upregulation of E-cadherin expression and overexpression of proinflammatory cytokines (TNFα, IL-1ß, and IL-6) in HOSE cells. The epithelial differentiation may accelerate HOSE cells to inclusion body formation, a common site for ovarian cancer initiation and persistent exposure to OCPs creates a chronic inflammatory microenvironment that may promote the neoplastic transformation of HOSE cells within the inclusion cyst.

Investigation of obesogenic effects of hexachlorobenzene, DDT and DDE in male rats.

Obesity has become a very important public health problem and is increasing globally. Genetics, individual and environmental factors play roles in the etiology of this complex disorder. Recently, several environmental pollutants have been suggested to have obesogenic activities. Peroxisome proliferator activating receptor gamma (PPARγ), uncoupling protein-1 (UCP1) and their expression in white adipose tissue (WAT) and brown adipose tissue (BAT) play key roles in adipogenesis. UCP3 and irisin were reported to play roles in non-shivering thermogenesis. Our primary aim was to investigate obesogenic effects of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in rats. In addition, thermoregulatory effects of HCB, DDT and DDE were also investigated by analyzing the levels of Ucp3 and irisin. Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups as control, HCB, DDT and DDE. Animals were administered with organochlorine pesticides (OCPs; 5 mg/kg bw) by oral gavage every other day for five weeks. At the end of the experimental period, the animals were sacrificed, BAT and WAT samples were collected to analyze Pparγ, Ucp1 and Ucp3 levels. Moreover, skeletal muscle samples were collected to examine Ucp3 and irisin levels. Serum glucose, cholesterol and triglyceride levels were also determined. Body weight and core temperature of the animals were not significantly affected by any of the OCP administration. Serum glucose, cholesterol and triglyceride levels were similar among the experimental groups. Pparγ expression was significantly elevated by HCB administration only in WAT (p < 0.05). On the other hand, both Pparγ and Ucp1 expressions were diminished in WAT and BAT (p < 0.01) by DDT treatment, while in WAT, DDE significantly decreased Pparγ expression without altering its expression in BAT (p < 0.001). Ucp3 and irisin levels in skeletal muscle were not altered. Our findings show that both DDT and DDE reduce the browning of WAT by suppressing white adipocytes and thus may have obesogenic activity in male rats without altering thermoregulation. In addition, HCB, DDT and DDE-induced alterations in expression of Pparγ and Ucp1 in WAT implicates differential regulation of adipogenic processes.

Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury.

OBJECITVIE: To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen (APAP)-induced hepatotoxicity. METHODS: Totally 90 Kunming mice were randomly divided into 10 groups according to body weight (9 mice for each group). The mice in the normal control and model (vehicle control) groups were administered sodium carboxymethyl cellulose (CMC-Na, 0.5%) only. Administration groups were pretreated with high and low-dose dry dandelion extract (1,000 or 500 g fresh herb dried and then decocted into 120 mL solution, DDE-H and DDE-L); low-, medium- and high-dose dandelion juice (250, 500, 1,000 g/120 mL, DJ-L, DJ-M, and DJ-H); fresh dandelions evaporation juice water (120 mL, DEJW); dry dandelion extract dissolved by pure water (1 kg/120 mL, DDED-PW); dry dandelion extract dissolved by DEJW (120 g/120 mL, DDED-DEJW) by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight; after that, except normal control group, all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury. Twenty hours after APAP administration, serum and liver tissue were collected and serum alanine aminotransferase (AST), aspartate transaminase (ALT), alkaline phosphatase (AKP), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activities were quantified by biochemical kits; tumor necrosis factor (TNF-α), interleukin (IL)-2, and IL-1 ß contents in liver tissue were determined by enzyme linked immunosorbent assay kits. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining; TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation. The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid-2-related factor 2 (Nrf-2), caspase-9, B-cell leukemia/lymphoma 2 (Bcl-2), Bax and p-JNK were determined by Western blot analysis. RESULTS: Pretreatment with fresh dandelion juice (FDJ, including DJ-L, DJ-M, DJ-H, DEJW and DDED-DEJW) significantly decreased the levels of serum ALT, AST, AKP, TNF-α and IL-1ß compared with vehicle control group (P<0.05 or P<0.01). Additionally, compared with the vehicle control group, FDJ decreased the levels of hepatic MDA and restored GSH levels and SOD activity in livers (P<0.05 or P<0.01). FDJ inhibited the overexpression of pro-inflammatory factors including cyclooxygenase-2 and inducible nitric oxide synthase in the liver tissues (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that FDJ pretreatment inhibited activation of apoptotic signaling pathways via decreasing of Bax, and caspase-9 and JNK protein expression, and inhibited activation of JNK pathway (P<0.05 or P<0.01). Liver histopathological observation provided further evidence that FDJ pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration and congestion. CONCLUSIONS: FDJ pretreatment protects against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway, and the effect of fresh dandelion extracts was superior to dried dandelion extracts in APAP hepatotoxicity model mice.

Estimated postnatal p,p'-DDT and p,p'-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children.

BACKGROUND: Children are exposed to p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children's exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age. METHODS: We used data from a birth cohort (n = 290) of the Tohoku Study of Child Development. p,p'-DDT and p,p'-DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0-6 months, 6-12 months, 12-24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models. RESULTS: We found no significant association between levels of p,p'-DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimated p,p'-DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimated p,p'-DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0-6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6-12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12-24 months exposure period. CONCLUSION: In this study of Japanese children, estimated postnatal p,p'-DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that early-life exposure to p,p'-DDE may be associated with higher BMI during childhood.

Residues of legacy organochlorine pesticides and DDT metabolites in highly consumed fish from the polluted Guanabara Bay, Brazil: distribution and assessment of human health risk.

Organochlorine (OCP) pesticides were determined in samples of sardine (Sardinella brasiliensis), whitemouth croaker (Micropogonias furnieri), and mullet (Mugil liza) from Guanabara Bay (state of Rio de Janeiro, Brazil). OCP concentrations and fish consumption were linked with acceptable daily intake values in order to assess the human health risk for the Brazilian population. The total concentrations of OCPs (Σ OCP) was 6.6 ng/g f.w., 7.5 ng/g f.w., and 2.8 ng/g f.w. for sardines, corvina, and mullet, respectively. There was a significant difference (P < 0.05) among the species related to o,p'-DDD and o,p'-DDT concentrations. Both DDT-related compounds were 5 and 76 times more abundant in sardines than in whitemouth croaker and mullet. Newly discovered DDT metabolite, o-Cl-DDMU, was frequently detected in the fish. None of the samples exceeded the maximum limits for acceptable levels of OCP residues. According to the data of average intake of Brazilian population, none of three species exceeded toxicological parameter. The investigated fishes are considered as safe for human consumption in regard to exposure of the studied OCPs. However, fish may be a intake source of OCP metabolites such as o-Cl-DDMU whose toxicity is still unknown.

Organochlorine pesticides induce inflammation, ROS production, and DNA damage in human epithelial ovary cells: An in vitro study.

Although the etiology of ovarian cancer is not clear, certain factors are implicated in this disease, such as ovulation, gonadotropic and steroid hormones, growth factors, cytokines, environmental agents, etc. Epidemiological studies have proven environmental exposure to pesticides with an increased risk of Epithelial Ovarian Cancer (EOC); however, the molecular mechanism underlying the carcinogenic effects of pesticides in human ovary remains poorly understood. The present study aimed to study the pro-inflammatory response of organochlorine pesticides (OCPs) namely ß-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethylene (DDE) and Dieldrin following exposure to human ovary surface epithelial cells (HOSE) for risk prediction of epithelial ovarian cancer. We found high level of Reactive oxygen species (ROS) production and DNA damage along with up-regulation of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, nuclear factor kappa B (NF-kB) and cyclooxygenase (COX)-2 expression in OCPs treated HOSE cells compared to control (DMSO). The result of the present study suggests that ß-HCH, DDE, and Dieldrin exposure induce ROS and pro-inflammatory response as well as DNA damage in HOSE cells. These various results show that OCPs may account for the neoplastic transformation of HOSE cells in the ovary.

Occurrence of organochlorine pesticides and polychlorinated biphenyls in sediment and fish in Cau Hai lagoon of Central Vietnam: Human health risk assessment.

This is the first study on polychlorinated biphenyls (PCBs) in fish from the Cau Hai lagoon, a part of the largest coastal lagoon in Southeast Asia. Seven selected PCB congeners and organochlorine pesticides in sediments and edible fish tissues were quantified by GC-MS. The sum of ICES-7 PCB and DDTs concentrations in fish species consumed regularly and of economic value were in ranges 26-43 ng g-1 lw and 182-277 ng g-1 lw, respectively. The ratio between the parent DDT compound and the sum of metabolites, DDE and DDD, was most of the time smaller than 1, suggesting primarily an historical contamination of the lagoon. An agglomerative hierarchical clustering indicates sites located in the north-western part of the Cau Hai lagoon were characterized by above-average concentrations of DDE and DDT. Comparing to previous data, a large decrease in ∑DDT residues can be seen over the past 20 years.

Snow buntings (Plectrophenax nivealis) as bio-indicators for exposure differences to legacy and emerging persistent organic pollutants from the Arctic terrestrial environment on Svalbard.

Eggs of snow buntings (Plectrophenax nivealis) were applied as a bio-indicator to examine differences in exposure to legacy persistent organic pollutants (POPs) and perflouroalkyl subtances (PFAS) from the terrestrial environment surrounding the settlements of Longyearbyen, Barentsburg and Pyramiden on Svalbard, Norway. Significantly higher concentrations of summed polychlorinated biphenyls (sumPCB7) in eggs collected from Barentsburg (2980 ng/g lipid weight (lw)) and Pyramiden (3860 ng/g lw) compared to Longyearbyen (96 ng/g lw) are attributed to local sources of PCBs within these settlements. Similar findings were observed for p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) where higher median concentrations observed in Pyramiden (173 ng/g lw) and Barentsburg (75 ng/g lw) compared to Longyearbyen (48 ng/g lw) may be influenced by guano inputs from breeding seabird populations, although other point sources cannot be ruled out. Concentrations of perfluorooctane sulphonate (PFOS) and several perfluorinated carboxylic acids (PFCAs) in snow bunting eggs were found to be statistically higher in the populated settlements of Longyearbyen and Barentsburg compared to the abandoned Pyramiden. Narrow foraging ranges of snow buntings during breeding season was useful in assessing point sources of exposure for PCBs and PFAS at particular sites with extreme differences observed between nest locations. SumPCB7 concentrations ranged from 2 µg/g ww to below detection limits between nest sites located less than a kilometer from each other in Pyramiden. Similar findings were observed in Longyearbyen, where several PFCAs ranged from 2 to 55 times higher between nest sites with similar spatial distances. These findings indicate that snow buntings can be a useful bio-indicator offering high spatial resolution for contaminant source apportionment in terrestrial environments on Svalbard.

Cytokine expression and lymphocyte proliferative capacity in diseased harbor porpoises (Phocoena phocoena) - Biomarkers for health assessment in wildlife cetaceans.

Harbor porpoises (Phocoena phocoena) in the North and Baltic Seas are exposed to anthropogenic influences including acoustic stress and environmental contaminants. In order to evaluate immune responses in healthy and diseased harbor porpoise cells, cytokine expression analyses and lymphocyte proliferation assays, together with toxicological analyses were performed in stranded and bycaught animals as well as in animals kept in permanent human care. Severely diseased harbor porpoises showed a reduced proliferative capacity of peripheral blood lymphocytes together with diminished transcription of transforming growth factor-ß and tumor necrosis factor-α compared to healthy controls. Toxicological analyses revealed accumulation of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) in harbor porpoise blood samples. Correlation analyses between blood organochlorine levels and immune parameters revealed no direct effects of xenobiotics upon lymphocyte proliferation or cytokine transcription, respectively. Results reveal an impaired function of peripheral blood leukocytes in severely diseased harbor porpoises, indicating immune exhaustion and increased disease susceptibility.

Excretion kinetics of three dominant organochlorine compounds in human milk within the first 6 months postpartum.

Breastfeeding is a specific and important way for women to eliminate harmful substances accumulated in body. Hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), and 2,2-bis(p-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) are dominant organochlorine compounds(OCCs) and persistent organic pollutants (POPs) accumulated in human being. Although a 6-month breastfeeding was suggested by the World Health Organization (WHO), the excretion characteristics of OCCs in human milk during the first 6-month lactation remain controversial. The main purpose of this study was to continuously monitor the three dominant OCC concentrations and reveal their elimination characteristic in human milk within the first 6-month lactation. To do that, with one sample per month, during their first 6-month lactation, human milk samples were continuously collected from 40 mothers after their first birth. The result showed that the concentrations of the three OCCs in human milk during the lactation continuously decreased from 51.7 to 39.9 µg/kg milk lipids for HCB, from 136.5 to 84.8 µg/kg milk lipids for ß-HCH, and from 307.3 to 192 µg/kg milk lipids, respectively. The excretion kinetics of each compound in milk lipids fitted zero-order kinetics during the 6-month lactation. The excretion rate of the three OCCs was approximately 3% per month for HCB and 7% per month for the other two compounds during the lactation, with tdec 1/2 of 13 months for HCB, 7.5 months for ß-HCH, and 8 months for p,p'-DDE. The excretion rate of the target compounds depended on initial deposited levels, compound properties, and exposure or input source.

Biodegradability and ecological safety assessment of Stenotrophomonas sp. DDT-1 in the DDT-contaminated soil.

The biodegradability and ecological safety assessment of the previously isolated DDT-degrading bacterial strain Stenotrophomonas sp. DDT-1 were investigated in the DDT-contaminated soil under laboratory and field conditions. Under laboratory conditions, the degradation rates of fresh p,p'-DDT in soil were enhanced by 2.0-3.0-fold with the introduction of the strain DDT-1 compared to those of the control treatments. A similar enhancement in the dissipation of DDTs (p,p'-DDT, p,p'-DDE, p,p'-DDD, and o,p'-DDT) in the aged DDT-contaminated field plot soils resulted from the inoculation with this strain. Meanwhile, the degradation rates of DDTs increased by 2.9-5.5- and 2.8-7.6-fold in the inoculated greenhouse and open field soils, respectively, after field demonstration application of strain DDT-1 preparation. Moreover, no significant differences in the soil enzyme activity, microbial functional diversity, and bacterial community structure were observed between the inoculated and un-inoculated field soils, but several soil microbial genera exhibited some fluctuations in abundance. It is concluded that strain DDT-1 could accelerate the removal of DDTs residues in field soils, and furthermore, its inoculation was ecologically safe.

Transcriptome signatures of p,p´-DDE-induced liver damage in Mus spretus mice.

The use of DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) in some countries, although regulated, is contributing to an increased worldwide risk of exposure to this organochlorine pesticide or its derivative p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene]. Many studies have associated p,p'-DDE exposure to type 2 diabetes, obesity and alterations of the reproductive system, but their molecular mechanisms of toxicity remain poorly understood. We have addressed this issue by using commercial microarrays based on probes for the entire Mus musculus genome to determine the hepatic transcriptional signatures of p,p'-DDE in the phylogenetically close mouse species Mus spretus. High-stringency hybridization conditions and analysis assured reliable results, which were also verified, in part, by qRT-PCR, immunoblotting and/or enzymatic activity. Our data linked 198 deregulated genes to mitochondrial dysfunction and perturbations of central signaling pathways (kinases, lipids, and retinoic acid) leading to enhanced lipogenesis and aerobic glycolysis, inflammation, cell proliferation and testosterone catabolism and excretion. Alterations of transcript levels of genes encoding enzymes involved in testosterone catabolism and excretion would explain the relationships established between p,p´-DDE exposure and reproductive disorders, obesity and diabetes. Further studies will help to fully understand the molecular basis of p,p´-DDE molecular toxicity in liver and reproductive organs, to identify effective exposure biomarkers and perhaps to design efficient p,p'-DDE exposure counteractive strategies.