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Dichlorodiphenyldichloroethylene (DDE) is a chemical compound formed by the loss of hydrogen chloride (dehydrohalogenation) from DDT, of which it is one of the more common breakdown products. Due to DDT's massive prevalence in society and agriculture during the mid 20th century, DDT and DDE are still widely seen in animal tissue samples. DDE is particularly dangerous because it is fat-soluble like other organochlorines; thus, it is rarely excreted from the body, and concentrations tend to increase throughout life. The major exception is the excretion of DDE in breast milk, which transfers a substantial portion of the mother's DDE burden to the young animal or child. Along with accumulation over an organism's lifetime, this stability leads to bioaccumulation in the environment, which amplifies DDE's negative effects. |
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InChI=1S/C14H8Cl4/c15-11-5-1-9(2-6-11)13(14(17)18)10-3-7-12(16)8-4-10/h1-8H |
UCNVFOCBFJOQAL-UHFFFAOYSA-N |
ClC(Cl)=C(C1=CC=C(Cl)C=C1)C1=CC=C(Cl)C=C1 |
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persistent organic pollutant
Any environmental contaminant that is resistant to environmental degradation through photolytic, biological or chemical processes. Such substances can have significant impact on health and the environment, as they persist in the environment, bioaccumulate in animal tissue and so biomagnify in food chains.
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human xenobiotic metabolite
Any human metabolite produced by metabolism of a xenobiotic compound in humans.
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View more via ChEBI Ontology
1-chloro-4-[2,2-dichloro-1-(4-chlorophenyl)ethenyl]benzene
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1,1'-(2,2-dichloroethene-1,1-diyl)bis(4-chlorobenzene)
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IUPAC
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1,1-bis-(4-chlorophenyl)-2,2-dichloroethene
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ChEBI
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1,1-dichloro-2,2-bis(4'-chlorophenyl)ethylene
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ChEBI
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1,1-Dichloro-2,2-bis(4'-chlorophenyl)ethylene
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KEGG COMPOUND
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1,1-Dichloro-2,2-bis(4-chlorophenyl)ethylene
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KEGG COMPOUND
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1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene
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UniProt
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2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene
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SUBMITTER
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4,4'-DDE
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ChemIDplus
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DDE
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KEGG COMPOUND
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p,p'-(Dichlorodiphenyl)-2,2-dichloroethylene
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ChemIDplus
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p,p'-DDE
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ChemIDplus
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1913355
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Reaxys Registry Number
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Reaxys
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72-55-9
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CAS Registry Number
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KEGG COMPOUND
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72-55-9
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CAS Registry Number
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NIST Chemistry WebBook
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72-55-9
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CAS Registry Number
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ChemIDplus
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Cortés-Montoya V, Ortiz-Robles CD, Rivera-Maya OB, Palacios-Valladares JR, Ramirez-Gutierrez EF, Calderón-Aranda ES (2023) The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice. Toxicology 493, 153554 [PubMed:37236336] [show Abstract] 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-1β 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-β1, 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-1β secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1β secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1β secretion process, as the NLRP3 activation, deserves further study. | Jiang J, He B, Wei Y, Cui J, Zhang Q, Liu X, Liu D, Wang P, Zhou Z (2022) The toxic effects of combined exposure of chlorpyrifos and p, p'-DDE to zebrafish (Danio rerio) and tissue bioaccumulation. Aquatic toxicology (Amsterdam, Netherlands) 248, 106194 [PubMed:35623197] [show Abstract] Pesticides are widely used and frequently detected in the environment. The evaluation on the toxic effects of the co-exposure of two or more pesticides or related metabolites could reflect the real situation of the exposing risks. In this study, zebrafish was used as a model to investigate the potential toxic interactions of chlorpyrifos and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) on the survival rate, oxidative stress response and neurotoxicity, as well as their bioaccumulation and distribution in tissues. Co-exposure of chlorpyrifos and p,p'-DDE resulted in significant additive acute toxic effects on adult zebrafish with model deviation ratio (MDR) = 1.64. Both 7-day short-term at 1% LC50 and 35-day long-term at 0.5% LC50 co-exposure of chlorpyrifos with p,p'-DDE (50 and 100 µg/L) significantly reduced the survival rate of zebrafish colony to 75 and 82.5%. Co-exposure of chlorpyrifos and p,p'-DDE contributed to increased activity of antioxidant enzyme CAT, SOD and GST and excessive MDA generation, and decreased activity of CarE, CYP450 and AChE, compared with either single exposure of them. In co-exposure, the bioaccumulation of chlorpyrifos and p,p'-DDE was significantly different from the single exposure group. Overall, this study unraveled the potential toxic interaction of chlorpyrifos and p,p'-DDE on zebrafish and provided reference for environmental risk assessment of pesticide mixture. | Li S, Shao W, Wang C, Wang L, Xia R, Yao S, Du M, Ji X, Chu H, Zhang Z, Wang M, Wang SL (2021) Identification of common genetic variants associated with serum concentrations of p, p'-DDE in non-occupational populations in eastern China. Environment international 152, 106507 [PubMed:33756427] [show Abstract] Dichlorodiphenyldichloroethylene (DDE) is the major and most stable toxic metabolite of dichlorodiphenyltrichloroethane (DDT), a well-known organochlorine pesticide banned worldwide in the 1980s. However, it remains easy to detect in humans, and internal levels vary widely among individuals. In the present study, a genome-wide association study (GWAS) (511 subjects) and two replications (812 and 1030 subjects) were performed in non-occupational populations in eastern China. An estimated dietary intake (EDI) of p, p'-DDT and p, p'-DDE was calculated by a food frequency questionnaire (FFQ) and the determination of 195 food and 85 drinking water samples. In addition, functional verifications of susceptible loci were performed by dual-luciferase reporter, immunoblotting and metabolic activity assays in vitro. p, p'-DDT and p, p'-DDE were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). A common loci rs3181842 (high linkage equilibrium with rs2279345) in CYP2B6 at 19p13.2 were found to be strongly associated with low serum levels of p, p'-DDE in this population in GWAS and were verified by two replications and combined analysis of 2353 subjects (P = 1.00 × 10-22). In addition, p, p'-DDE levels were significantly lower in subjects with the rs3181842 C allele than in those carrying the normal genotype, even in individuals with similar EDIs of p, p'-DDT. Furthermore, the rs3181842 C allele functionally led to low CYP2B6 expression and activity, resulting in a low metabolic capacity for the formation of p, p'-DDE from p, p'-DDT. The study highlighted that CYP2B6 variants were more relevant than environmental exposure to internal p, p'-DDE exposure, which is important information for DDT risk assessments. | Plouffe L, Bosson-Rieutort D, Madaniyazi L, Iwai-Shimada M, Nakai K, Tatsuta N, Nakayama SF, Verner MA (2020) 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. Environmental health : a global access science source 19, 49 [PubMed:32393266] [show Abstract]
BackgroundChildren 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.MethodsWe 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.ResultsWe 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.ConclusionIn 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. | Jugan J, Lind P, Salihovic S, Stubleski J, Kärrman A, Lind L, Merrill M (2020) SUN-571 The Associations Between p,p’-DDE Levels and Serum Levels of Lipoproteins and Their Subclasses in an Elderly Population Determined by Lipidomics Analysis Journal of the Endocrine Society 4, [PubMed Central:PMC7208238] [show Abstract] Abstract Low biodegradability and high lipophilicity of p,p’-dichlorodiphenyldichloroethylene (DDE), a metabolite of the insecticide DDT, leads to transport with lipids and accumulation in adipose tissue. This persistence allows for DDE to effect adipose tissue and lipid metabolism. A few small human studies have shown an association between DDE and blood lipids, although with some inconsistent conclusions. The aim of this study was to investigate the association between DDE exposure and altered levels of circulating lipids in a large human cohort. To evaluate the associations between DDE and human lipid profiles, plasma was collected from a subset of elderly Swedes in the Prospective Investigation of the Vasculature of Uppsala Seniors (PIVUS) cohort who were free from lipid lowering medication (n = 571). DDE concentrations in plasma were measured using high-throughput solid phase extraction and gas chromatography-high resolution mass spectrometry. Lipidomic analysis of plasma was performed with nuclear magnetic resonance spectroscopy. Linear models of lipids and DDE were statistically adjusted for sex and body mass index. Detectable levels of DDE were found in the plasma samples of all subjects. With elevated DDE levels, the comprehensive lipoprotein profile showed an elevation in total concentration of all diameters of very low density lipoprotein (VLDL) (p<0.001), low density lipoprotein (LDL) (p<0.008), intermediate density lipoprotein (IDL) (p<0.02), and in small high density lipoprotein (HDL) (p<0.05). Triglycerides and DDE were associated to varying degrees in lipoproteins (IDL > VLDL > LDL > HDL) and within total serum (p<0.005). DDE levels were positively associated with cholesterol and cholesterol ester levels only in VLDL and LDL (p<0.05) and with apolipoprotein B (p<0.0009). The positive associations observed between each lipoprotein class and elevated DDE support previous data suggesting that DDE interacts with lipoproteins within plasma. We speculate that both physio-chemical and biological mechanisms may explain why DDE does not uniformly associate with lipids across lipoproteins. | Jugan J, Lind PM, Salihovic S, Stubleski J, Kärrman A, Lind L, La Merrill MA (2020) The associations between p,p'-DDE levels and plasma levels of lipoproteins and their subclasses in an elderly population determined by analysis of lipoprotein content. Lipids in health and disease 19, 249 [PubMed:33287856] [show Abstract]
BackgroundLipoproteins at aberrant levels are known to play a role in cardiovascular disease. The metabolite of the insecticide dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), physically associates with lipids and accumulates in adipose tissue. Little is known about which lipoproteins associate with p,p'-DDE. An association between p,p'-DDE exposure and altered levels of circulating lipids was assessed in a large human cohort using a detailed analysis of lipoprotein content.MethodsPlasma samples were collected from the subset of 75-year old Swedes in the Prospective Investigation of the Vasculature of Uppsala Seniors (PIVUS) cohort who were not prescribed lipid lowering medication (n = 571). p,p'-DDE concentrations in plasma were measured using high-throughput solid phase extraction and gas chromatography-high resolution mass spectrometry. Analysis of plasma lipoprotein content was performed with nuclear magnetic resonance spectroscopy.ResultsDetectable levels of p,p'-DDE were found in the plasma samples of all subjects. Elevated p,p'-DDE levels were associated with increased concentrations of lipoproteins of all diameters, with the exception of high density lipoprotein (HDL) of diameters between 14.3 nm-10.9 nm. Of the lipoprotein constituents, triglycerides were most uniformly associated with elevated p,p'-DDE across lipoproteins. p,p'-DDE was furthermore associated with apolipoprotein B, but not apolipoprotein A1.ConclusionsThe positive associations observed between each lipoprotein class and elevated p,p'-DDE support previous data suggesting that p,p'-DDE interacts with lipoproteins within plasma. It is speculated that both physio-chemical and biological mechanisms may explain why p,p'-DDE does not uniformly associate with lipids across lipoproteins. | Pavlíková N, Daniel P, Šrámek J, Jelínek M, Šrámková V, Němcová V, Balušíková K, Halada P, Kovář J (2019) Upregulation of vitamin D-binding protein is associated with changes in insulin production in pancreatic beta-cells exposed to p,p'-DDT and p,p'-DDE. Scientific reports 9, 18026 [PubMed:31792309] [show Abstract] Persistent organochlorine pollutants (POPs) gradually accumulate in the human organism due to their presence in the environment. Some studies have described a correlation between the level of POPs in the human body and the incidence of diabetes, but we know little about the direct effect of POPs on pancreatic beta-cells. We exposed pancreatic beta-cells INS1E to non-lethal concentrations of p,p'-DDT (1,1'-(2,2,2-Trichloroethane-1,1-diyl)bis(4-chlorobenzene)) and p,p'-DDE (1,1'-(2,2-dichloroethene-1,1-diyl)bis(4-chlorobenzene)) for 1 month, and assessed changes in protein expression and the intracellular insulin level. 2-D electrophoresis revealed 6 proteins with changed expression in cells exposed to p,p'-DDT or p,p'-DDE. One of the detected proteins - vitamin D-binding protein (VDBP) - was upregulated in both cells exposed to p,p'-DDT, and cells exposed to p,p'-DDE. Both exposures to pollutants reduced the intracellular level of insulin mRNA, proinsulin, and insulin monomer; p,p'-DDT also slightly reduced the level of hexameric insulin. Overexpression of VDBP caused by the stable transfection of beta-cells with the gene for VDBP decreased both the proinsulin and hexameric insulin level in beta-cells similarly to the reduction detected in cells exposed to p,p'-DDT. Our data suggest that in the cells exposed to p,p'-DDT and p,p'-DDE, the increased VDBP protein level decreased the proinsulin expression in an unknown mechanism. | Nwachukwu JC, Srinivasan S, Bruno NE, Nowak J, Wright NJ, Minutolo F, Rangarajan ES, Izard T, Yao XQ, Grant BJ, Kojetin DJ, Elemento O, Katzenellenbogen JA, Nettles KW (2017) Systems Structural Biology Analysis of Ligand Effects on ERα Predicts Cellular Response to Environmental Estrogens and Anti-hormone Therapies. Cell chemical biology 24, 35-45 [PubMed:28042045] [show Abstract] Environmental estrogens and anti-hormone therapies for breast cancer have diverse tissue- and signaling-pathway-selective outcomes, but how estrogen receptor alpha (ERα) mediates this phenotypic diversity is poorly understood. We implemented a statistical approach to allow unbiased, parallel analyses of multiple crystal structures, and identified subtle perturbations of ERα structure by different synthetic and environmental estrogens. Many of these perturbations were in the sub-Å range, within the noise of the individual structures, but contributed significantly to the activities of synthetic and environmental estrogens. Combining structural perturbation data from many structures with quantitative cellular activity profiles of the ligands enabled identification of structural rules for ligand-specific allosteric signaling-predicting activity from structure. This approach provides a framework for understanding the diverse effects of environmental estrogens and for guiding iterative medicinal chemistry efforts to generate improved breast cancer therapies, an approach that can be applied to understanding other ligand-regulated allosteric signaling pathways. | Pérez-Maldonado IN, Trejo-Acevedo A, Orta-García ST, Ochoa-Martinez AC, Varela-Silva JA, Pérez-Vázquez FJ (2014) DDT and DDE concentrations in the blood of Mexican children residing in the southeastern region of Mexico. Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes 49, 87-93 [PubMed:24328540] [show Abstract] The aim of this study was to assess the levels of dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in the blood of children living in the southeastern region of Mexico. In this study, we found high levels of DDT and its principal metabolite (DDE) in the blood of children residing in the communities studied. The levels of total DDT found in our study ranged from 4,676.4 ng/g lipid to 64,245.2 ng/g lipid. All of the children in the study had detectable levels of DDT and/or DDE. In conclusion, our data indicate that children living within the study areas are exposed to high levels of DDT and DDE. Moreover, these results can be used as a trigger to revisit local policies on environmental exposures. | Nguyen PA, Trinh TH, Fukumitsu Y, Shimodaira J, Miyauchi K, Tokuda M, Kasai D, Masai E, Fukuda M (2013) Gene cluster and regulation system for 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE) degradation in Janibacter sp. TYM3221. Journal of bioscience and bioengineering 116, 91-100 [PubMed:23415487] [show Abstract] A DDE-degrading bacterium, Janibacter sp. TYM3221, is able to grow on biphenyl and degrades 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE) via a meta-ring cleavage pathway. The bphAa gene, encoding a biphenyl dioxygenase large subunit, was previously demonstrated to be involved in the degradation of DDE in TYM3221. The bph gene cluster, containing orf2 and bphDAaAbAcAdBCST was cloned and characterized. Reverse transcription-PCR (RT-PCR) analysis indicated that these genes were transcribed as an operon. The real-time RT-PCR on orf2, bphAa, bphC, and bphS suggest the presence of the inducible orf2 promoter (orf2p) and constitutive bphAa promoter (bphAap). The TYM3221 bphST conducted biphenyl-dependent inducible activation plus constitutive basal activation of orf2p and constitutive activation of bphAap in a rhodococcal host strain, Rhodococcus erythropolis IAM1399, suggesting that expression of the TYM3221 bph operon depends on the bphST-coded two-component regulatory system. Both of these promoters were also induced by the bphS1T1 of a biphenyl degrader, Rhodococcus jostii RHA1, and contained the 24-bp consensus sequences of RHA1 bphS1T1-dependent promoters. The replacement of RHA1 bphS1 with TYM3221 bphS in combination with RHA1 bphT1 suggests that TYM3221 bphS is responsible for low inducible and high constitutive activation of orf2p in IAM1399 by the TYM3221 bphST-system. Expression of bphAaAbAcAdBC in IAM1399 resulted in the transformation of DDE to the meta-ring cleavage product via 2,3-hydroxylation, suggesting that these genes are involved in DDE degradation. | Nguyen AT, Sato Y, Iwasaki T, Miyauchi K, Tokuda M, Kasai D, Masai E, Fukuda M (2011) Characterization of the 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE) degradation system in Janibacter sp. TYM3221. Enzyme and microbial technology 49, 532-539 [PubMed:22142728] [show Abstract] Bacterial degradation of 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE) has been previously reported, however, its degradation enzyme system has not been characterized. In this study, a DDE-degrading bacterium, Janibacter sp. TYM3221, was isolated and characterized. Transformation of DDE was demonstrated by TYM3211 resting cells grown in LB in the presence and absence of biphenyl. Gas chromatography-mass spectrometry analysis revealed five metabolites of DDE containing a meta-ring cleavage product and 4-chlorobenzoic acid, suggesting that TYM3221 degrades DDE to 4-chlorobenzoic acid via a meta-ring cleavage product. A gene cluster, bphAaAbAcAd, which codes for biphenyl dioxygenase subunits, was cloned from TYM3221. A mutant strain with a bphAa-gene inactivation did not grow on biphenyl, and showed no DDE degradation activity. These results indicate that in strain TYM3221, the bphAa-coded biphenyl dioxygenase is involved not only in the metabolism of biphenyl but also in the degradation of DDE. | Tiedeken JA, Ramsdell JS (2010) Zebrafish seizure model identifies p,p -DDE as the dominant contaminant of fetal California sea lions that accounts for synergistic activity with domoic acid. Environmental health perspectives 118, 545-551 (Source: SUBMITTER) [PubMed:20368122] [show Abstract]
BackgroundFetal poisoning of California sea lions (CSLs; Zalophus californianus) has been associated with exposure to the algal toxin domoic acid. These same sea lions accumulate a mixture of persistent environmental contaminants including pesticides and industrial products such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Developmental exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) and its stable metabolite 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p -DDE) has been shown to enhance domoic acid-induced seizures in zebrafish; however, the contribution of other co-occurring contaminants is unknown.ObjectiveWe formulated a mixture of contaminants to include PCBs, PBDEs, hexachlorocyclohexane (HCH), and chlordane at levels matching those reported for fetal CSL blubber to determine the impact of co-occurring persistent contaminants with p,p -DDE on chemically induced seizures in zebrafish as a model for the CSLs.MethodsEmbryos were exposed (6-30 hr postfertilization) to p,p -DDE in the presence or absence of a defined contaminant mixture prior to neurodevelopment via either bath exposure or embryo yolk sac microinjection. After brain maturation (7 days postfertilization), fish were exposed to a chemical convulsant, either pentylenetetrazole or domoic acid; resulting seizure behavior was then monitored and analyzed for changes, using cameras and behavioral tracking software.ResultsInduced seizure behavior did not differ significantly between subjects with embryonic exposure to a contaminant mixture and those exposed to p,p -DDE only.ConclusionThese studies demonstrate that p,p -DDE--in the absence of PCBs, HCH, chlordane, and PBDEs that co-occur in fetal sea lions--accounts for the synergistic activity that leads to greater sensitivity to domoic acid seizures. | Shabbir A, DiStasio S, Zhao J, Cardozo CP, Wolff MS, Caplan AJ (2005) Differential effects of the organochlorine pesticide DDT and its metabolite p,p'-DDE on p-glycoprotein activity and expression. Toxicology and applied pharmacology 203, 91-98 [PubMed:15710169] [show Abstract] 1,1-Bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) is an organochlorine pesticide. Its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethene (p,p'-DDE) is a persistent environmental contaminant and both compounds accumulate in animals. Because multidrug resistance transporters, such as p-glycoprotein, function as a defense against xenobiotic exposure, we analyzed the ability of DDT and p,p'-DDE to act as efflux modulators. Using a competitive intact cell assay based on the efflux of the fluorescent dye rhodamine 123, we found that DDT, but not p,p'-DDE, stimulated dye retention. Subsequent studies using verapamil as competitor suggested that DDT is a weak p-glycoprotein inhibitor. Further studies addressed the ability of DDT and p,p'-DDE to induce MDR1, the gene encoding p-glycoprotein. In HepG2 cells, we found that both compounds induced MDR1 by twofold to threefold. Similar results were observed in mouse liver after a single dose of p,p'-DDE, although some gender-specific induction differences were noted. By contrast, p,p'-DDE failed to induce MDR1 in HeLa cells, indicating some cell-specific effects for induction. Further expression studies demonstrated increased levels of the endoplasmic reticulum molecular chaperone, Bip, in response to DDT, but not p,p'-DDE. These results suggest that DDT, but not p,p'-DDE, induces an endoplasmic reticulum stress response. | Younglai EV, Holloway AC, Lim GE, Foster WG (2004) Synergistic effects between FSH and 1,1-dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE) on human granulosa cell aromatase activity. Human reproduction (Oxford, England) 19, 1089-1093 [PubMed:15070871] [show Abstract]
Background1,1-Dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE, DDE), a metabolite of DDT, is a persistent hormonally active environmental toxicant which has been found in human serum and follicular fluid. The objective of this study was to investigate the interaction between FSH and ppDDE on aromatase activity in primary cultures of human granulosa cells.MethodsGranulosa cells were obtained at the time of oocyte retrieval for IVF procedures and cultured in defined medium containing FSH and environmentally relevant concentrations of DDE. Aromatase activity was measured by incubating the cells with 1beta-[(3)H]androstenedione and measuring the release of (3)H(2)O.ResultsThe granulosa cell response to FSH was highly dependent on the basal level of aromatase activity (r = -0.703, P = 0.001, n = 17) with the highest activity occurring at low basal levels of aromatase activity. Enzyme activity was significantly stimulated at 100 ng DDE/ml. A synergistic effect on aromatizing activity was observed when cells were co-cultured with DDE and FSH.ConclusionsConcentrations of DDE similar to those present in human follicular fluid enhance basal and FSH-stimulated granulosa cell aromatizing enzyme activity. | Smeds A, Saukko P (2001) Identification and quantification of polychlorinated biphenyls and some endocrine disrupting pesticides in human adipose tissue from Finland. Chemosphere 44, 1463-1471 [PubMed:11513126] [show Abstract] Organochlorine pesticides and polychlorinated biphenyls (PCBs) were analysed in extracts of human adipose tissue. The samples consisted of abdominal, mammary, and perirenal fat tissue of 27 Finnish adult males and females. Lipids were separated from the low-molecular compounds by preparative gel permeation chromatography (GPC) and the extracts were further cleaned-up using Florisil chromatography. The compounds were analysed in the extracts by gas chromatography (GC) using electron capture detection and by GC-mass spectrometry in the selected ion monitoring mode. Of the 23 analysed pesticide residues only seven could be detected in the extracts. All the extracts contained the DDT metabolite 4,4'-DDE, hexachlorobenzene, and PCBs. Other compounds found in the extracts were 4,4'-DDT, 4,4'-DDD, pentachlorobenzene, and beta- and gamma-hexachlorocyclohexane (HCH). The antiandrogenic 4,4'-DDE was the most abundant pesticide with concentration levels ranging from 3.5 to 3229 ng/g lipids (ppb). The mean concentration of DDE was 567 ppb, of pesticides in all 1008 ppb and of PCBs 504 ppb. Several of the identified compounds have been shown to exhibit endocrine disrupting effects. Statistical analysis showed a positive age correlation of DDE in females and hexachlorobenzene in males. No statistically significant differences were found for concentrations of individual compounds between sexes. |
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