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Sample records for hexachlorocyclohexane dieldrin tcdd

  1. Differential estrogenic effects of the persistent organochlorine pesticides dieldrin, endosulfan, and lindane in primary neuronal cultures.

    Science.gov (United States)

    Briz, Víctor; Molina-Molina, José-Manuel; Sánchez-Redondo, Sara; Fernández, Mariana F; Grimalt, Joan O; Olea, Nicolás; Rodríguez-Farré, Eduard; Suñol, Cristina

    2011-04-01

    The organochlorine chemicals endosulfan, dieldrin, and γ-hexachlorocyclohexane (lindane) are persistent pesticides to which people are exposed mainly via diet. Their antagonism of the γ-aminobutyric acid-A (GABA(A)) receptor makes them convulsants. They are also endocrine disruptors because of their interaction with the estrogen receptor (ER). Here, we study the effects of dieldrin, endosulfan, and lindane on ERs in primary cultures of cortical neurons (CN) and cerebellar granule cells (CGC). All the compounds tested inhibited the binding of [(3)H]-estradiol to the ER in both CN and CGC, with dieldrin in CGC showing the highest affinity. We also determined the effects of the pesticides on protein kinase B (Akt) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation. Dieldrin and endosulfan increased Akt phosphorylation in CN, which was inhibited by the ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol. Instead, Akt and ERK1/2 phosphorylation induced by dieldrin in CGC was mediated by multiple activation of ERα, ERβ, and G protein-coupled receptor 30. Lindane did not activate these pathways, but it inhibited estradiol-mediated Akt and ERK1/2 activation. In CN, all the chemicals activated ERK1/2 through a mechanism involving GABA(A) and glutamate receptors. Long-term exposure to these pesticides reduced the levels of ERα, but not of ERβ. Moreover, extracts of CN treated with endosulfan, dieldrin, or lindane induced cell proliferation in MCF-7 human breast cancer-derived cells, whereas only extracts of CGC treated with dieldrin induced MCF-7 cell proliferation. Overall, the observed alterations on ER-mediated signaling and ER levels in neurons might contribute to the neurotoxicity of these organochlorine pesticides.

  2. Study of Dieldrin in Coralville Reservoir

    OpenAIRE

    Jeremy Smith

    2013-01-01

    Using existing experimental data taken over a period of roughly 12 years that documents the concentrations of dieldrin levels in the environment and fatty tissue of the fish, we construct a model of the total dieldrin concentration decline. Comparisons between the experimental data and speculative data can be made using calculus and elements of statistics in order to better understand the movement of dieldrin in the reservoir. Because of the potentially harmful exposure effects of dieldrin to...

  3. Differential uptake and translocation of β-HCH and dieldrin by several plant species from hydroponic medium.

    Science.gov (United States)

    Namiki, Sayuri; Otani, Takashi; Seike, Nobuyasu; Satoh, Shinobu

    2015-03-01

    To compare the uptake and translocation of hydrophobic organic chemicals by plant species, the authors performed uptake experiments with β-1,2,3,4,5,6-hexachlorocyclohexane (β-HCH) and 1,2,3,4,10,10-Hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-1,4-exo-5,8-dimethanonaphthalene (dieldrin) using 5 species: Hordeum vulgare, Glycine max, Solanum lycopersicum, Brassica oleracea, and Cucurbita pepo. The present study evaluated uptake ability using root concentration factor (RCF) and translocation ability by transpiration stream concentration factor (TSCF). The RCFs of β-HCH and dieldrin did not differ remarkably among species, except that the RCF of β-HCH in B. oleracea was high. The TSCFs of β-HCH and dieldrin were high in C. pepo, which was not superior in uptake as estimated by RCF. The TSCF of dieldrin in C. pepo was decreased in darkness and was markedly decreased by heating of roots. These results support the hypothesis that transport proteins produced in the root contribute to dieldrin translocation. In contrast, TSCF of β-HCH was not decreased by these treatments. Therefore, translocation of β-HCH might not need the contribution of transport proteins. It is possible that C. pepo has a certain function to transport hydrophobic organic chemicals smoothly in root tissues. © 2014 SETAC.

  4. Study of Dieldrin in Coralville Reservoir

    Directory of Open Access Journals (Sweden)

    Jeremy Smith

    2013-01-01

    Full Text Available Using existing experimental data taken over a period of roughly 12 years that documents the concentrations of dieldrin levels in the environment and fatty tissue of the fish, we construct a model of the total dieldrin concentration decline. Comparisons between the experimental data and speculative data can be made using calculus and elements of statistics in order to better understand the movement of dieldrin in the reservoir. Because of the potentially harmful exposure effects of dieldrin to humans as well as the environment, it is important to be able to predict when stability has been restored to the ecosystem.

  5. Toxicity and Metabolism of Dieldrin in Rats

    Science.gov (United States)

    Heath, D. F.; Vandekar, M.

    1964-01-01

    The main constituent of the insecticide dieldrin has been studied in male and female rats. The LD50s depend on the route of injection and, after intravenous infusion, on the rate of infusion. After oral injection of a 4% solution in arachis oil, deaths take place within six hours or from two to seven days later; but the first convulsion occurs at 40 min. over a wide range of doses. For further studies 36Cl-dieldrin was used. Absorption from the gastrointestinal tract varies with the vehicle and is via the portal vein, not the thoracic lymph duct. Distribution is initially general, but within a few hours of injection it is heavily in favour of fat. Excretion of 36Cl averages about 5% per day. It is markedly increased by a restriction of diet, which reduces the body fat. From the cannulated bile duct, excretion accelerates as the rat loses weight, exceeding 10% per day after a few days. Only 3% of the 36Cl is excreted as dieldrin unless the bile is cannulated, when 10% may be excreted. The remainder is in metabolites, 90% in the faeces and 10% in the urine. Many metabolites have been demonstrated but not identified. The most important, containing about 60% of the total 36Cl, is excreted in the bile, probably as a glucuronide and reconstituted in the intestine before being excreted in the faeces. From these findings one can interpret many of the toxic effects of dieldrin, including the effects of starvation on toxicity and the prolonged sensitization to a second dose (Barnes and Heath, 1964) in terms of the low solubility of dieldrin in water, its high solubility in fat, and its mobilization when fat is utilized. Toxic effects are related to the dieldrin mobilized; there is no need to postulate that dieldrin produces a long-lasting lesion in the central nervous system. The findings and conclusions are shown to be relevant to the toxic effects of dieldrin in man. PMID:14249895

  6. Cellular Localization of Dieldrin and Structure–Activity Relationship of Dieldrin Analogues in Dopaminergic Cells

    Science.gov (United States)

    Allen, Erin M. G.; Florang, Virginia R.; Davenport, Laurie L.; Jinsmaa, Yunden; Doorn, Jonathan A.

    2015-01-01

    The incidence of Parkinson’s disease (PD) correlates with environmental exposure to pesticides, such as the organochlorine insecticide, dieldrin. Previous studies found an increased concentration of the pesticide in the striatal region of the brains of PD patients and also that dieldrin adversely affects cellular processes associated with PD. These processes include mitochondrial function and reactive oxygen species production. However, the mechanism and specific cellular targets responsible for dieldrin-mediated cellular dysfunction and the structural components of dieldrin contributing to its toxicity (toxicophore) have not been fully defined. In order to identify the toxicophore of dieldrin, a structure–activity approach was used, with the toxicity profiles of numerous analogues of dieldrin (including aldrin, endrin, and cis-aldrin diol) assessed in PC6-3 cells. The MTT and lactate dehydrogenase (LDH) assays were used to monitor cell viability and membrane permeability after treatment with each compound. Cellular assays monitoring ROS production and extracellular dopamine metabolite levels were also used. Structure and stereochemistry for dieldrin were found to be very important for toxicity and other end points measured. Small changes in structure for dieldrin (e.g., comparison to the stereoisomer endrin) yielded significant differences in toxicity. Interestingly, the cis-diol metabolite of dieldrin was found to be significantly more toxic than the parent compound. Disruption of dopamine catabolism yielded elevated levels of the neurotoxin, 3,4-dihydroxyphenylacetaldehyde, for many organochlorines. Comparisons of the toxicity profiles for each dieldrin analogue indicated a structure-specific effect important for elucidating the mechanisms of dieldrin neurotoxicity. PMID:23763672

  7. Cellular localization of dieldrin and structure-activity relationship of dieldrin analogues in dopaminergic cells.

    Science.gov (United States)

    Allen, Erin M G; Florang, Virginia R; Davenport, Laurie L; Jinsmaa, Yunden; Doorn, Jonathan A

    2013-07-15

    The incidence of Parkinson's disease (PD) correlates with environmental exposure to pesticides, such as the organochlorine insecticide, dieldrin. Previous studies found an increased concentration of the pesticide in the striatal region of the brains of PD patients and also that dieldrin adversely affects cellular processes associated with PD. These processes include mitochondrial function and reactive oxygen species production. However, the mechanism and specific cellular targets responsible for dieldrin-mediated cellular dysfunction and the structural components of dieldrin contributing to its toxicity (toxicophore) have not been fully defined. In order to identify the toxicophore of dieldrin, a structure-activity approach was used, with the toxicity profiles of numerous analogues of dieldrin (including aldrin, endrin, and cis-aldrin diol) assessed in PC6-3 cells. The MTT and lactate dehydrogenase (LDH) assays were used to monitor cell viability and membrane permeability after treatment with each compound. Cellular assays monitoring ROS production and extracellular dopamine metabolite levels were also used. Structure and stereochemistry for dieldrin were found to be very important for toxicity and other end points measured. Small changes in structure for dieldrin (e.g., comparison to the stereoisomer endrin) yielded significant differences in toxicity. Interestingly, the cis-diol metabolite of dieldrin was found to be significantly more toxic than the parent compound. Disruption of dopamine catabolism yielded elevated levels of the neurotoxin, 3,4-dihydroxyphenylacetaldehyde, for many organochlorines. Comparisons of the toxicity profiles for each dieldrin analogue indicated a structure-specific effect important for elucidating the mechanisms of dieldrin neurotoxicity.

  8. The toxicity of dieldrin to man

    Science.gov (United States)

    Hayes, Wayland J.

    1959-01-01

    Increased use of dieldrin for malaria control has been caused by several factors, including sporadic resistance of some vectors to DDT. Poisoning of spray-men by dieldrin has been recognized in five widely separated countries and reported informally from several others. In some cases illness has recurred months after the last exposure. Observations of antimalaria programmes in Kenya, Tanganyika, Indonesia, India (Bombay State), and Iran and a review of the relevant literature have shown that the hazard associated with dieldrin is proportional to the degree of workers' exposure as determined by concentration of spray, area of bare skin, duration of contact, and lack of hygiene. Measurements of workers' exposure and a review of toxicity by different routes incriminates skin contamination as the greatest hazard under practical conditions. It is considered that dieldrin should not be used without justification; if it is required, then certain individual and group protective measures listed in this paper may minimize, but not necessarily eliminate, the risk. The author enumerates certain features of the toxicology of dieldrin which require intensive research. PMID:14400335

  9. Gezondheidsrisico's in verband met het werken met Dieldrin : een onderzoek

    NARCIS (Netherlands)

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.L.

    1989-01-01

    Op basis van gegevens verkregen uit een oriënterende werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan dieldrin en een literatuurstudie naar mogelijke schadelijke eigenschappen van dieldrin op het reproduktiesysteem en/of nageslacht

  10. 40 CFR 129.100 - Aldrin/dieldrin.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Aldrin/dieldrin. 129.100 Section 129... POLLUTANT EFFLUENT STANDARDS Toxic Pollutant Effluent Standards and Prohibitions § 129.100 Aldrin/dieldrin. (a) Specialized definitions. (1) Aldrin/Dieldrin manufacturer means a manufacturer, excluding any...

  11. Some Toxic Effects of Dieldrin in Rats

    Science.gov (United States)

    Barnes, J. M.; Heath, D. F.

    1964-01-01

    The oral toxicity of dieldrin in rats depends upon its concentration in the vehicle (arachis oil). It is increased by a previous restriction of diet, leading to a loss of weight. Two equal doses given within three weeks of each other are more toxic than the sum of the two given as a single dose. PMID:14249896

  12. Dieldrin uptake and translocation in plants growing in hydroponic medium.

    Science.gov (United States)

    Murano, Hirotatsu; Otani, Takashi; Seike, Nobuyasu; Sakai, Mizuki

    2010-01-01

    It has been known that the Cucurbitaceae family takes up a large amount of persistent organic pollutants from soils and that the translocation of those compounds in cucurbits is higher than those in non-cucurbits. To understand the persistent organic pollutant uptake mechanisms of plant species, we compared the dieldrin absorption and transportation potentials of several plants in hydroponic medium. Sorghum (Sorghum vulgare Moench), sunflower (Helianthus annuus L.), soybean (Glycine max), komatsuna (Brassica rapa var. peruviridis), white-flowered gourd (Lagenaria siceraria var. hispida), cucumber (Cucumis sativus L.), and zucchini (Cucurbita pepo L.) were grown in a dieldrin-added hydroponic medium for 10 d, and then the amount of dieldrin in their shoots and roots was measured. All of the roots contained dieldrin, whereas only the cucurbits (white-flowered gourd, cucumber, and zucchini) contained considerable amounts of dieldrin in their shoots. The dieldrin uptake to the roots depended on the concentration of the n-hexane soluble components in the roots, regardless of whether the dieldrin in the roots was translocated to shoots or not. The dieldrin uptake from the solution to the roots was thought to be due to a passive response, such as adsorption on the roots. The translocation of dieldrin from the roots to the shoots was probably through the xylems. The amounts of dieldrin in the shoots per transpiration rates were higher for cucurbits than for non-cucurbits. It seems likely that cucurbits have uptake mechanisms for hydrophobic organic chemicals.

  13. Dieldrin-resistance in Culex pipiens fatigans in Malaya

    Science.gov (United States)

    Wharton, R. H.

    1958-01-01

    Resistance to insecticides in Culex pipiens fatigans has already been reported from two areas in Malaya. In Penang two years' use of BHC as a larvicide resulted in the development of a strain which was found to have acquired a tenfold resistance to BHC, and also to dieldrin to which it had not been exposed. In Singapore, when larval control became unsatisfactory after 6 months' use of a dieldrin emulsion, laboratory experiments confirmed that active resistance to dieldrin had developed. The present observations report the finding of two further dieldrin-BHC resistant strains of C. p. fatigans in Malaya, but differ from the previous reports in that resistance, in one strain at least, was developed as a result of house-spraying with dieldrin against adult mosquitos. In this strain resistance to dieldrin was about 100 times in both adults and larvae, resistance to gamma-BHC in larvae was about 20 times, while resistance to DDT was slight. PMID:13536808

  14. Reductive dechlorination of hexachlorocyclohexane (HCH) isomers in soil under anaerobic conditions

    NARCIS (Netherlands)

    Middeldorp, P.J.M.; Doesburg, van W.C.J.; Schraa, G.; Stams, A.J.M.

    2005-01-01

    The biological anaerobic reductive dechlorination of -hexachlorocyclohexane under methanogenic conditions was tested in a number of contaminated soil samples from two locations in the Netherlands. Soils from a heavily polluted location showed rapid dechlorination of -hexachlorocyclohexane to benzene

  15. Reductive dechlorination of hexachlorocyclohexane (HCH) isomers in soil under anaerobic conditions

    NARCIS (Netherlands)

    Middeldorp, P.J.M.; Doesburg, van W.C.J.; Schraa, G.; Stams, A.J.M.

    2005-01-01

    The biological anaerobic reductive dechlorination of -hexachlorocyclohexane under methanogenic conditions was tested in a number of contaminated soil samples from two locations in the Netherlands. Soils from a heavily polluted location showed rapid dechlorination of -hexachlorocyclohexane to benzene

  16. Gezondheidsrisico's in verband met het werken met Dieldrin : een onderzoek

    OpenAIRE

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A; Zielhuis, R.L.

    1989-01-01

    Op basis van gegevens verkregen uit een oriënterende werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan dieldrin en een literatuurstudie naar mogelijke schadelijke eigenschappen van dieldrin op het reproduktiesysteem en/of nageslacht (6000S-AIST-73/2) is een evaluatie gemaakt van het gezondheidsrisico van werken met dieldrin. Er zijn aanwijzingen voor reproduktierisico's m.b.t. tot blootstelling van volwassenen. Voor vrouwen in de vru...

  17. Dieldrin poisoning in dogs: relation to obesity and treatment

    Science.gov (United States)

    Keane, William T.; Zavon, Mitchell R.; Witherup, Samuel H.

    1969-01-01

    Keane, William T., Zavon, Mitchell R., and Witherup, Samuel H. (1969).Brit. J. industr. Med.,26, 338-341. Dieldrin poisoning in dogs: relation to obesity and treatment. The time interval required for poisoning to result in mammals from the prolonged absorption of a relatively constant amount of dieldrin, a chlorinated hydrocarbon insecticide, is directly related to obesity. This relationship should be applicable regardless of the route of absorption of dieldrin (ingestion, inhalation, or percutaneous). Forced feeding of a high calorific value food appears to have a place in the treatment of dieldrin poisoning and, by extension, in the treatment of poisoning from many other chlorinated hydrocarbon insecticides. PMID:5346832

  18. Reproduction, growth, and tissue residues of deer fed dieldrin

    Science.gov (United States)

    Murphy, D.A.; Korschgen, L.J.

    1970-01-01

    Feeding tests were conducted from January, 1966, to January, 1969, to ascertain the effects of daily ingestions of sublethal amounts of dieldrin on white-tailed deer (Odocoileus virginianus). Groups of deer on 0 ppm dieldrin (controls), 5 ppm, and 25 ppm dieldrin were maintained at these respective levels, as were their progeny. Treated food was readily accepted. Dieldrin intoxication was not observed, and 9 of 10 animals of each group survived 3 years of treatment. No differences in conception or in utero mortality were found between groups. Fawns from dieldrin-fed does were smaller at birth and greater post-partum mortality occurred. Fertility of male progeny was not affected. Growth was slower and remained reduced in dieldrin-treated females which were immature when the study began. Hematologic values and serum protein concentrations were not significantly (P > 0.05) related to treatment. Liver/body weight ratios were significantly (P < 0.05) larger for the 25-ppm-dieldrin group. Pituitary glands were smaller and thyroids were larger in dieldrin-fed deer. Weight gains of fawns were significantly (P < 0.05) reduced 2 of 3 years in dieldrin-treated groups. Placental transfer of dieldrin occurred. Whole milk from does fed 25 ppm dieldrin contained residues of 17 ppm. Residue levels in brain, liver, and thigh muscle tissues showed no evidence of increasing with length of treatment, but showed definite relationships to levels of dieldrin in daily diets. Nursing fawns had higher residues in brain tissues than did older deer on 5 ppm a d 25 ppm dieldrin. Highest brain residues (12.60 and 12.10 ppm, wet weight) occurred in fawns only a few days of age at death. Equilibrium between ingestion and storage or excretion of dieldrin occurred prior to 200 days and continued until nearly 1,100 days. There was no evidence of a sharp decline in residues after a long period of continued dosage. Daily ingestion of 100 and 200 ppm of dieldrin proved fatal to yearling male deer at 27

  19. Epoxidation of aldrin to exo-dieldrin by soil bacteria.

    Science.gov (United States)

    Ferguson, J A; Korte, F

    1977-01-01

    Twenty-two strains of soil bacteria, including representatives of the genera Bacillus, Micromonospora, Mycobacterium, Nocardia, Streptomyces, Thermoactinomyces, and Pseudomonas and 10 unidentified gram-negative, motile, rod-shaped bacteria, were shown to degrade aldrin to its epoxide dieldrin. In every case, the exo-stereoisomer of dieldrin was produced exclusively. PMID:407844

  20. Heme oxygenase-1 induction by dieldrin in dopaminergic cells.

    Science.gov (United States)

    Kim, Do Kyung; Kim, Jae-Sung; Kim, Ji-Eun; Kim, Sung-Jun; Lee, Jung-Sup; Kim, Dae-Joong; Son, Jin H; Chun, Hong Sung

    2005-04-04

    We investigated the transcriptional events and signaling pathways involved in the induction of heme oxygenase-1 (HO-1) by dieldrin, an environmental risk factor of Parkinson's disease, in a dopaminergic neuronal cells (SN4741). Dieldrin exposure caused dose-dependent and time-dependent induction of heme oxygenase activity and HO-1 protein expression. Deletional and mutational analyses showed that the 5' distal enhancers, E1 and E2, mediate dieldrin-induced HO-1 gene transcription, and the AP-1 DNA binding sites in the E2 enhancer are critical for E2-mediated HO-1 gene activation. Furthermore, both the p38 and JNK mitogen-activated protein kinase pathways are utilized for HO-1 transcriptional activation by dieldrin. HO-1 inhibitor, ZnPP IX reduced the expression of HO-1 but enhanced the cytotoxicity induced by dieldrin.

  1. TCDD adsorbed on silica as a model for TCDD contaminated soils: Evidence for suppression of humoral immunity in mice.

    Science.gov (United States)

    Kaplan, Barbara L F; Crawford, Robert B; Kovalova, Natalia; Arencibia, Amaya; Kim, Seong Su; Pinnavaia, Thomas J; Boyd, Stephen A; Teppen, Brian J; Kaminski, Norbert E

    2011-04-11

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the prototypical aryl hydrocarbon receptor (AhR) ligand, exhibits immune suppression in vivo and in vitro. Suppression of primary humoral immune responses in particular has been well characterized as one of the most sensitive functional immune endpoints in animals treated with TCDD. Previous studies have used purified TCDD to elucidate the mechanisms by which TCDD and dioxin-like compounds (DLC) impair IgM production by B cells, but did not represent the route by which animals and humans are likely to be exposed environmentally. In the studies reported here, mice were treated with TCDD adsorbed onto a well-defined synthetic silica phase of known purity and physical properties, followed by sensitization with sheep erythrocytes to initiate a humoral immune response. We found that surfactant-templated mesoporous forms of amorphous silica provided an ideal combination of purity, dispersibility and textural properties for immobilizing TCDD. TCDD-adsorbed silica distributed to the spleen and liver after oral administration as assessed by induction of cyp1a1 gene expression. Most notably, TCDD delivered in the adsorbed state on amorphous silica and as a solute in corn oil (CO) produced similar suppression of the anti-sheep red blood cell immunoglobulin M antibody forming cell (sRBC IgM AFC) response at equivalent doses of TCDD. These results suggest that TCDD immobilized on silicate particles found in soils distributes to the spleen and suppresses humoral immunity.

  2. Relationship between dieldrin uptake in cucumber and solvent-extractable residue in soil.

    Science.gov (United States)

    Sakai, Mizuki; Seike, Nobuyasu; Murano, Hirotatsu; Otani, Takashi

    2009-12-09

    To prevent the distribution of cucumbers with dieldrin contamination exceeding the limit set by the Japanese Food Sanitation Law, the extraction solvent for dieldrin-contaminated soil was selected prior to cultivation so that the dieldrin residue level in cucumber could be predicted. The exhaustive extraction from soil could not explain the dieldrin uptake by cucumber plants. However, significant correlation (R(2) = 0.966, P dieldrin concentrations in cucumber and dieldrin concentrations extracted with 50% (v/v) methanol-water solution from soils. This was a result of the phytoavailability of dieldrin to the cucumber plants. The extractability of soil dieldrin with the methanol-water solution decreased as the organic carbon content in the soils increased. This suggested that a 50% (v/v) methanol-water solution is the optimal solution for predicting dieldrin concentrations in cucumbers by soil analysis.

  3. Rat embryonic palatal shelves respond to TCDD in organ culture

    Energy Technology Data Exchange (ETDEWEB)

    Abbott, B.D.; Birnbaum, L.S. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1990-05-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a highly toxic environmental contaminant, is teratogenic in mice, inducing cleft palate (CP) and hydronephrosis at doses which are not overtly maternally or embryo toxic. Palatal shelves of embryonic mice respond to TCDD, both in vivo and in organ culture, with altered differentiation of medial epithelial cells. By contrast, in the rat TCDD produces substantial maternal, embryonic, and fetal toxicity, including fetal lethality, with few malformations. In this study the possible effects of maternal toxicity on induction of cleft palate were eliminated by exposure of embryonic rat palatal shelves in organ culture. The shelves were examined for specific TCDD-induced alterations in differentiation of the medial cells. On Gestation Day (GD) 14 or 15 palatal shelves from embryonic F344 rats were placed in organ culture for 2 to 3 days (IMEM:F12 medium, 5% FBS, 0.1% DMSO) containing 0, 1 x 10(-8), 1 x 10(-9), 1 x 10(-10), or 5 x 10(-11) M TCDD. The medial epithelial peridermal cells degenerated on shelves exposed to control media or 5 x 10(-11) M TCDD. Exposure to 10(-10), 10(-9), and 10(-8) M TCDD inhibited this degeneration in 20, 36, and 60% of the shelves, respectively, and was statistically significant at the two highest doses. A normally occurring decrease in (3H)TdR incorporation was inhibited in some GD 15 shelves cultured with 10(-10) and 10(-9) M TCDD. The medial cells of TCDD-exposed shelves continued to express high levels of immunohistochemically detected EGF receptors. The altered differentiation of rat medial epithelium is similar to that reported for TCDD-exposed mouse medial cells in vivo and in vitro. However, in order to obtain these responses, the cultured rat shelves require much higher concentrations of TCDD than the mouse shelves.

  4. Limited PCB antagonism of TCDD-induced malformations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Morrissey, R.E.; Harris, M.W.; Diliberto, J.J.; Birnbaum, L.S.

    1992-01-01

    Mice used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day with hexachlorobiphenyl (HCB) and/or with tetrachlorodibenzo-p-dioxin (TCDD) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. At the doses used in the study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with = or > 250 mg HCB/kg. HCB did not induce cleft palate at a dose of 1000 mg/kg, but did induce increases in hydronephrosis and hydroureter at 500 and 1000 mg/kg. Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15 microgram TCDD/kg combined with 125-500 mg HCB/kg. The window for antagonism of hydronephrosis (incidence and severity) appeared narrower (15 microgram TCDD/kg + 500 mg HCB/kg). HCB induced increases (3 fold) in EROD activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of TCDD teratogenicity by HCB would be consistent with control by Ah receptor. (Copyright (c) 1992 Elsevier Science Publishers B.V.)

  5. Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: A case study with the organochlorine pesticide dieldrin

    OpenAIRE

    Martyniuk, Christopher J.; Doperalski, Nicholas J.; Kroll, Kevin J.; Barber, David S.; Denslow, Nancy D.

    2012-01-01

    Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3 mg dieldrin/kg feed in a 2 month feeding exposure (August–October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin ne...

  6. Dieldrin uptake by vegetable crops grown in contaminated soils.

    Science.gov (United States)

    Donnarumma, Lucia; Pompi, Valter; Faraci, Alessandro; Conte, Elisa

    2009-06-01

    The aim of these trials was to study the distribution of dieldrin in soil and its translocation to roots and the aerial parts of vegetable crops grown in greenhouses and fields. The main objectives were to characterize dieldrin accumulation in plant tissues in relation to the levels of soil contamination; uptake capability among plants belonging to different species, varieties and cultivars. The presence of the contaminant was quantified by gas chromatography-electron capture detector (GC-ECD) and confirmed by gas chromatography-mass spectrometer (GC-MS). The results showed a translocation of residues in cucurbitaceous fruits and flowers confirming that zucchini, cucumber and melon are crops with high uptake capability. The maximum level of dieldrin residue at 0.01 mg/kg was found to be a threshold value to safeguard the quality production of cucurbits. Tomato, lettuce and celery were identified as substitute crops to grow in contaminated fields.

  7. Dieldrin resistance in the malaria vector Anopheles gambiae in Ghana.

    Science.gov (United States)

    Brooke, B D; Hunt, R H; Matambo, T S; Koekemoer, L L; Van Wyk, P; Coetzee, M

    2006-09-01

    Anopheles gambiae Giles s.s. (Diptera: Culicidae) is one of the principal vectors of malaria in the Ashanti region of central Ghana. High levels of resistance to dieldrin were recorded in a wild-caught sample from Obuasi (south of Kumasi) as well as a laboratory colony established using material from the wild population. Cytogenetic analysis of wild-caught and laboratory samples revealed chromosomal polymorphism for inversions 2La and 2Rb. Although inversion 2La has previously been shown to be associated with dieldrin resistance in certain other laboratory strains originating from West Africa, there was no obvious association between inversion karyotype assortment and the resistance phenotype in the Obuasi population. In addition, polymerase chain reaction analysis indicated the presence of the alanine296 to glycine mutation in the GABA (gamma amino-butyric acid) receptor (which has been mapped to a chromosomal position within inversion 2La). This mutation has previously been shown to be associated with dieldrin resistance in the same An. gambiae laboratory strains of West African origin. Our data show only a weak association between the dieldrin resistance phenotype and the presence of this mutation, suggesting that another dieldrin resistance mechanism is operational in the Obuasi population. Biochemical and synergist exposure assays suggest a metabolic component, probably mediated by monooxygenase P450 enzymes. We conclude that dieldrin resistance in the An. gambiae population of the Obuasi region occurs at a high level - most likely in the absence of selection - and that control of the resistance phenotype is polyfactorial and must include components other than mutations in the GABA receptor locus.

  8. DDT-resistance and dieldrin-resistance in Anopheles quadrimaculatus*

    Science.gov (United States)

    Davidson, G.

    1963-01-01

    The nature and mode of inheritance of both DDT-resistance and dieldrin-resistance in Anopheles quadrimaculatus from the United States of America have been studied. Dieldrin-resistance is shown to be dependent on a single, semi-dominant, genetic factor, and DDT-resistance on a single, recessive one, though the expression of this latter factor is to some extent dependent on the genetic background. Both resistances can occur in the same mosquito but can be separated, thus indicating the independent nature of the two genetic factors involved. PMID:14056269

  9. Distribution of TCDD in blood constituents of rats and humans

    Science.gov (United States)

    Wirsing, J. M.; Weber, L. W.; Kettrup, A. A.; Rozman, Karl K.

    1995-10-01

    Whole blood or plasma from male human volunteers or pooled from male Sprague-Dawley rats was incubated with varying amounts of 3H-2,3,7,8-tetrachlorodibenzo-p-dioxin (3H-TCDD). Blood was separated into cellular, protein and lipoprotein fractions by centrifugation. The distribution of 3H-TCDD between lipoproteins and plasma proteins was independent of 3H-TCDD concentration in the range of 65 fmol-1 nmol/ml plasma. The distribution of 3H-TCDD between the various lipoprotein fractions depended only on their relative content of total cholesterol plus triglycerides. The partitioning of 3H- TCDD between lipoproteins and plasma proteins was inversely proportional, whereas the distribution between the cellular fraction and the lipoproteins was directly proportional to the total plasma cholesterol plus triglyceride content. As a consequence of species differences in blood composition, the major part of 3H-TCDD-associated radioactivity was recovered from lipoproteins in human blood but from erythrocytes in rat blood. A mathematical description of the distribution of TCDD between blood components is presented.

  10. TCDD disrupts posterior palatogenesis and causes cleft palate.

    Science.gov (United States)

    Yamada, Tomohiro; Hirata, Azumi; Sasabe, Eri; Yoshimura, Tomohide; Ohno, Seiji; Kitamura, Naoya; Yamamoto, Tetsuya

    2014-01-01

    Dioxins (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) cause cleft palate at a high rate. A post-fusional split may contribute to the pathogenesis, and tissue fragility may be a concern. The objective of this study was to investigate the effects of TCDD on the palatal epithelium, bone and muscle, which contribute to tissue integrity. ICR mice (10-12 weeks old) were used. TCDD was administered on E12.5 at 40 mg/kg. Immunohistochemical staining for AhR, ER-α, laminin, collagen IV, osteopontin, Runx2, MyoD, and desmin were performed. Furthermore, western blot analysis for osteopontin, Runx2, MyoD, and desmin were performed to evaluate protein expression in the palatal tissue. Immunohistologically, there was little difference in the collagen IV and laminin localization in the palatal epithelium between control versus TCDD-treated mice. Runx2 and osteopontin immunoreactivity decreased in the TCDD-treated palatal bone, and MyoD and desmin decreased in the TCDD-treated palatal muscle. AhR and ER-α immunoreactivity were localized to the normal palatal bone, but ER-α was diminished in the TCDD-treated palate. On western blot analysis, Runx2, MyoD, and desmin were all downregulated in the TCDD-treated palate. TCDD may suppress palatal osteogenesis and myogenesis via AhR, and cause cleft palates via a post-fusional split mechanism, in addition to a failure of palatal fusion.

  11. Cross-resistance between dieldrin and fipronil in German cockroach (Dictyoptera: Blattellidae).

    Science.gov (United States)

    Kristensen, Michael; Hansen, Kenneth Klingenberg; Jensen, Karl-Martin Vagn

    2005-08-01

    The toxicity of fipronil and dieldrin was determined in one susceptible laboratory strain and seven insecticide-resistant field-collected strains of Blattella germanica (L). The Zo960302 and Ga021001 strains were 1,270- and 2,030-fold resistant to dieldrin and 15- and 14-fold resistant to fipronil. The Su960304 and Od010803 strains were 15- and 13-fold resistant to dieldrin and two- and four-fold resistant to fipronil. Three strains showed no or a low level of resistance to dieldrin and fipronil. Crosses were performed between the susceptible strain Danish Pest Infestation Laboratory (DPIL)-SUS and the resistant strains Zo960302 and Su960304 and resistance to dieldrin and fipronil were intermediate compared with the susceptible and the resistant strains. Backcrosses to both of the parental strains showed cosegregation of dieldrin and fipronil resistance. The toxicity of dieldrin and fipronil was correlated when compared at LD50, and 93% of the observed variation in LD50 of fipronil can be ascribed to variation among predictions based on the value of LD50 of dieldrin. The frequency of the A302S substitution in the resistance to dieldrin (Rdl) gene in the highly dieldrin- and fipronil-resistant strains Zo960302 and Ga021001 and the moderately resistant Su960304 was 0.97, 1.0, and 0.38, respectively. We consider the connection between the frequency of the Rdl mutation and dieldrin and fipronil resistance a causal connection and not merely a coincidence.

  12. The effect of DDT and dieldrin on myelinated nerve fibres

    NARCIS (Netherlands)

    Bercken, J. van den

    1972-01-01

    The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10−4 M) was found to be exclusi

  13. The effect of DDT and dieldrin on myelinated nerve fibres

    NARCIS (Netherlands)

    Bercken, J. van den

    The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10−4 M) was found to be

  14. The effect of in vitro dieldrin exposure on the rat paraoxonase 1 (pon1) promoter.

    Science.gov (United States)

    Dail, Mary Beth; Pickin, Rebecca; Crow, John Allen; Chambers, Janice E

    2014-05-01

    The legacy organochlorine insecticide, dieldrin, is still found in soil and accumulation in individuals is possible. Paraoxonase 1 hydrolyzes the oxon metabolites of organophosphorus insecticides, as well as other substrates. Putative binding sites for pregnane X receptor (PXR) exist in the paraoxonase promoter, and studies have indicated that dieldrin can activate PXR-regulated gene expression. We examined rat paraoxonase promoter activity in the presence of dieldrin alone or combined with nuclear receptors (NRs). In vitro dieldrin concentrations from 10 to 100 µM significantly increased (p dieldrin can increase paraoxonase promoter activity in the presence of NRs. To our knowledge, this is the first report of dieldrin increasing paraoxonase promoter activity. Since many organochlorine insecticides are in the same chemical class as dieldrin, these results could be typical of other bioaccumulative persistent pollutants. © 2014 Wiley Periodicals, Inc.

  15. COMPUTATION MODELING OF TCDD DISRUPTION OF B CELL TERMINAL DIFFERENTIATION

    Science.gov (United States)

    In this study, we established a computational model describing the molecular circuit underlying B cell terminal differentiation and how TCDD may affect this process by impinging upon various molecular targets.

  16. The immunotoxic effects of dual exposure to PCP and TCDD.

    Science.gov (United States)

    Chen, Hsiu-Min; Lee, Yu-Hsuan; Chen, Rong-Jane; Chiu, Hui-Wen; Wang, Bour-Jr; Wang, Ying-Jan

    2013-11-25

    Pentachlorophenol (PCP) was a commonly used fungicide, herbicide, insecticide, and bactericide in industrial, agricultural, and domestic settings; however, it was also contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). It has been reported that technical grade PCP had immunosuppressive effects and that the immune system was the major target of PCDD/PCDFs toxicity. Although the immune response after exposure to PCP or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied, the toxic effects of exposure to both PCP and TCDD have not yet been reported. The aim of this study was to evaluate the effects on immune cells from mice intraperitoneally immunized with OVA and subsequently treated with PCP or TCDD alone or in combination by gavage. The animals were terminated on day 7 and 14, and the spleen and plasma samples were collected for immunotoxicity evaluation. The numbers and populations of splenocytes, T cell-derived cytokines produced by splenocytes, splenocyte-generated cytotoxicity and OVA-specific antibodies in plasma were investigated. Our results indicate that the spleen/body weight ratio and splenocyte number was reduced by TCDD alone; in addition, this reduction was enhanced when TCDD was combined with PCP. Exposure to TCDD alone or in conjunction with PCP suppressed many ovalbumin (OVA)-stimulated cytokines, including IL-2, IFN-γ, IL-4, IL-5, and IL-10. Furthermore, the immunoglobulins IgG and IgM were suppressed in mice administered by PCP alone, but the suppressive effects were greater in mice treated with TCDD alone or in combination with PCP. Co-exposure to PCP and TCDD resulted in an antagonistic effect on TCDD-induced suppression of IFN-γ and IL-10. Our results demonstrate that PCP alone is immunotoxic, regardless of the presence of TCDD. PCP led to mild changes in cytokine secretion, and it compromised splenocyte-generated cytotoxicity and IgM and IgG antibody production on day 7. The finding

  17. Sphingobium baderi sp. nov., isolated from a hexachlorocyclohexane dump site.

    Science.gov (United States)

    Kaur, Jasvinder; Moskalikova, Hana; Niharika, Neha; Sedlackova, Miroslava; Hampl, Ales; Damborsky, Jiri; Prokop, Zbynek; Lal, Rup

    2013-02-01

    A Gram-stain-negative, rod-shaped and white-coloured bacterial strain, designated LL03(T), was isolated from hexachlorocyclohexane-contaminated soil at Spolana Neratovice, Czech Republic, where lindane was formerly produced. Strain LL03(T) was found to be a degrader of α-, γ- and δ-isomers of hexachlorocyclohexane, although no significant degradation activity was observed for the β-isomer. A neighbour-joining tree based on 16S rRNA gene sequences showed that strain LL03(T) occupied a distinct phylogenetic position in the Sphingobium cluster, showing the highest similarity with Sphingobium wenxiniae JZ-1(T) (99.2 %). The DNA G+C content of strain LL03(T) was 67.0 mol%. DNA-DNA relatedness values of strain LL03(T) with its close phylogenetic neighbours were below the threshold level of 70 %, supporting its identification as a representative of a novel species of the genus Sphingobium. The predominant respiratory quinone was ubiquinone Q-10. The polar lipid profile of strain LL03(T) also corresponded to those reported for other Sphingobium species (phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylmonomethylethanolamine and sphingoglycolipid), supporting its identification as a member of the genus Sphingobium. Spermidine was identified as the major polyamine. The predominant fatty acids were 16 : 0, summed feature 3 (16 : 1ω7c and/or 16 : 1ω6c), summed feature 8 (18 : 1ω7c and/or 18 : 1ω6c) and 14 : 0 2-OH. The polar lipid pattern, the presence of spermidine and ubiquinone Q-10, the predominance of the cellular fatty acids C(18 : 1)ω7c, C(16 : 0) and C(14 : 0) 2-OH and the G+C content of the genomic DNA supported the affiliation of the strain to the genus Sphingobium. The results obtained after DNA-DNA hybridization, biochemical and physiological tests clearly distinguished it from closely related species of the genus Sphingobium. Therefore, strain LL03(T

  18. Bacterial Bio-Resources for Remediation of Hexachlorocyclohexane

    Directory of Open Access Journals (Sweden)

    María J. Amoroso

    2012-11-01

    Full Text Available In the last few decades, highly toxic organic compounds like the organochlorine pesticide (OP hexachlorocyclohexane (HCH have been released into the environment. All HCH isomers are acutely toxic to mammals. Although nowadays its use is restricted or completely banned in most countries, it continues posing serious environmental and health concerns. Since HCH toxicity is well known, it is imperative to develop methods to remove it from the environment. Bioremediation technologies, which use microorganisms and/or plants to degrade toxic contaminants, have become the focus of interest. Microorganisms play a significant role in the transformation and degradation of xenobiotic compounds. Many Gram-negative bacteria have been reported to have metabolic abilities to attack HCH. For instance, several Sphingomonas strains have been reported to degrade the pesticide. On the other hand, among Gram-positive microorganisms, actinobacteria have a great potential for biodegradation of organic and inorganic toxic compounds. This review compiles and updates the information available on bacterial removal of HCH, particularly by Streptomyces strains, a prolific genus of actinobacteria. A brief account on the persistence and deleterious effects of these pollutant chemical is also given.

  19. Pontibacter lucknowensis sp. nov., isolated from a hexachlorocyclohexane dump site.

    Science.gov (United States)

    Dwivedi, Vatsala; Niharika, Neha; Lal, Rup

    2013-01-01

    A Gram-negative, orange-pigmented, rod-shaped, motile and aerobic bacterial strain designated DM9(T) was isolated from hexachlorocyclohexane (HCH)-contaminated soil (Lucknow, India) and its taxonomic position was determined using a polyphasic approach. 16S rRNA gene sequence analysis showed that the isolate belonged to the phylum Bacteroidetes and confirmed its placement in the genus Pontibacter, with sequence similarity ranging from 93.92 to 96.21 % with other members of the genus Pontibacter. The major cellular fatty acids of the novel strain were iso-C(17 : 0) 3-OH (6.00 %), iso-C(15 : 0) (21.54 %) and summed feature 4 (comprising C(17 : 1) iso I/anteiso B; 32.3 %). The polar lipid profile of strain DM9(T) showed the presence of phosphatidylethanolamine, an unidentified aminophospholipid, two unknown aminolipids and four unknown polar lipids. Strain DM9(T) contained MK-7 as the predominant menaquinone and its DNA G+C content was 49.2 mol%. sym-Homospermidine was the major polyamine observed in the cell. The results obtained on the basis of phenotypic characteristics, phylogenetic analysis, biochemical and physiological tests clearly distinguished DM9(T) from closely related members of the genus Pontibacter. It is proposed that DM9(T) represents a novel species, Pontibacter lucknowensis sp. nov.; the type strain is DM9(T) (= CCM 7955(T) = MTCC 11079(T)).

  20. Sphingobium czechense sp. nov., isolated from a hexachlorocyclohexane dump site.

    Science.gov (United States)

    Niharika, Neha; Moskalikova, Hana; Kaur, Jasvinder; Khan, Fazlurrahman; Sedlackova, Miroslava; Hampl, Ales; Damborsky, Jiri; Prokop, Zbynek; Lal, Rup

    2013-02-01

    A yellow-pigmented bacterial strain, designated LL01(T), was isolated from hexachlorocyclohexane (HCH)-contaminated soil at Spolana Neratovice, a former Czech producer of lindane. A neighbour-joining tree based on 16S rRNA gene sequences showed that strain LL01(T) occupied a distinct phylogenetic position in the Sphingobium cluster, showing highest similarity to Sphingobium rhizovicinum CC-FH12-1(T) (98.5 %). The DNA G+C content of strain LL01(T) was 66.1 mol%. The predominant respiratory pigment was ubiquinone Q-10. The polar lipid profile of strain LL01(T) also corresponded to those reported for other Sphingobium species (phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine, sphingoglycolipids), supporting its identification as a member of the genus Sphingobium. Spermidine was the major polyamine observed. The results obtained from DNA-DNA hybridization and biochemical and physiological tests clearly distinguished strain LL01(T) from closely related species of the genus Sphingobium. Therefore, strain LL01(T) represents a novel species of the genus Sphingobium, for which the name Sphingobium czechense sp. nov. is proposed (type strain LL01(T) = CCM 7979(T) = DSM 25410(T)).

  1. The efficacy of dieldrin against wool destroying insect

    Directory of Open Access Journals (Sweden)

    P. K. Ayappa

    1961-04-01

    Full Text Available The efficacy of dieldrin as a protection against the wool destroying insects. Anthrenus flavipes Lec. (wooly bear and Tinea pellionella Linn. (case bearing clothes moth has been investigated. In very low concentrations (0.02-0.05percent on the weight of fabric, the insecticides offers adequate protection against both the insects. the effectiveness of treatment is not impaired by laundering (12 times or dry-cleaning (12 times. The resistance to laundering and dry-cleaning is not, however, as satisfactory when the insecticide is applied from solution. The economics of utilization of dieldrin as a protectant against the wool destroying insects has been discussed in relation to DDT, and it is shown that the former insecticide is much less expensive.

  2. Toxicological profile of organochlorines aldrin and dieldrin: an Indian perspective.

    Science.gov (United States)

    Sharma, Noopur; Garg, Deepali; Deb, Roumi; Samtani, Ratika

    2017-09-15

    Several epidemiological studies have suggested various environmental factors as a possible cause for increased incidence of various abnormalities. Of the various environmental contaminants, the most prevalent and the most discussed are the endocrine disrupting chemicals. Contact of such disruptors with humans has become inevitable today. They are cosmopolitan and present from agriculture to industrial sectors, even in day-to-day consumer products. Aldrin and dieldrin belong to one such class of substances which are known to have a toxic effect on various physiological systems of the human body. Despite an imposed ban on their manufacture and commercial use, these pesticides could still be detected in probable areas of consumption like agriculture. The present review discusses the known possible toxic effects of aldrin and dieldrin and their current existence in the ecosystem across India.

  3. Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis.

    Science.gov (United States)

    Kanthasamy, Anumantha G; Kitazawa, Masashi; Kanthasamy, Arthi; Anantharam, Vellareddy

    2005-08-01

    Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.

  4. Theoretical study of γ-hexachlorocyclohexane and β-hexachlorocyclohexane isomers interaction with surface groups of activated carbon model.

    Science.gov (United States)

    Enriquez-Victorero, Carlos; Hernández-Valdés, Daniel; Montero-Alejo, Ana Lilian; Durimel, Axelle; Gaspard, Sarra; Jáuregui-Haza, Ulises

    2014-06-01

    Activated carbon (AC) is employed in drinking water purification without almost any knowledge about the adsorption mechanism of persistent organic pollutants (POPs) onto it. Hexachlorocyclohexane (HCH) is an organochlorinated contaminant present in water and soils of banana crops production zones of the Caribbean. The most relevant isomers of HCH are γ-HCH and β-HCH, both with great environmental persistence. A theoretical study of the influence of AC surface groups (SGs) on HCH adsorption is done in order to help to understand the process and may lead to improve the AC selection process. A simplified AC model consisting of naphthalene with a functional group was used to assess the influence of SGs over the adsorption process. The Multiple Minima Hypersurface (MMH) methodology was employed to study γ-HCH and β-HCH interactions with different AC SGs (hydroxyl and carboxyl) under different hydration and pH conditions. The results obtained showed that association of HCH with SGs preferentially occurs between the axial protons of HCH and SG's oxygen atom, and the most favorable interactions occurring with charged SGs. An increase in carboxylic SGs content is proposed to enhance HCH adsorption onto AC under neutral pH conditions. Finally, this work presents an inexpensive computer aided methodology for preselecting activated carbon SGs content for the removal of a given compound.

  5. Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast.

    Science.gov (United States)

    Gaytán, Brandon D; Loguinov, Alex V; Lantz, Stephen R; Lerot, Jan-Michael; Denslow, Nancy D; Vulpe, Chris D

    2013-04-01

    Exposure to organochlorinated pesticides such as dieldrin has been linked to Parkinson's and Alzheimer's diseases, endocrine disruption, and cancer, but the cellular and molecular mechanisms of toxicity behind these effects remain largely unknown. Here we demonstrate, using a functional genomics approach in the model eukaryote Saccharomyces cerevisiae, that dieldrin alters leucine availability. This model is supported by multiple lines of congruent evidence: (1) mutants defective in amino acid signaling or transport are sensitive to dieldrin, which is reversed by the addition of exogenous leucine; (2) dieldrin sensitivity of wild-type or mutant strains is dependent upon leucine concentration in the media; (3) overexpression of proteins that increase intracellular leucine confer resistance to dieldrin; (4) leucine uptake is inhibited in the presence of dieldrin; and (5) dieldrin induces the amino acid starvation response. Additionally, we demonstrate that appropriate negative regulation of the Ras/protein kinase A pathway, along with an intact pyruvate dehydrogenase complex, is required for dieldrin tolerance. Many yeast genes described in this study have human orthologs that may modulate dieldrin toxicity in humans.

  6. Environmental fate of TCDD and Agent Orange and bioavailability to troops in Vietnam

    Energy Technology Data Exchange (ETDEWEB)

    Karch, N.J.; Watkins, D.K.; Ginevan, M.E. [Exponent, Inc., Washington, DC (United States); Young, A.L. [Oklahoma Univ., Norman, OK (United States)

    2004-09-15

    This paper reviews the environmental fate of Agent Orange and the contaminant, 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), and discusses how this affects the bioavailability of TCDD for ground troops in Vietnam.

  7. Acinetobacter indicus sp. nov., isolated from a hexachlorocyclohexane dump site.

    Science.gov (United States)

    Malhotra, Jaya; Anand, Shailly; Jindal, Swati; Rajagopal, Raman; Lal, Rup

    2012-12-01

    The taxonomic position of a Gram-negative, non-motile, oxidase negative and catalase positive strain, A648(T), isolated from a hexachlorocyclohexane (HCH) dump site located in Lucknow, India, was ascertained by using a polyphasic approach. A comparative analysis of a partial sequence of the rpoB gene and the 16S rRNA gene sequence revealed that strain A648(T) belonged to the genus Acinetobacter. DNA-DNA relatedness values between strain A648(T) and other closely related members (16S rRNA gene sequence similarity greater than 97%), namely Acinetobacter radioresistens DSM 6976(T), A. venetianus ATCC 31012(T), A. baumannii LMG 1041(T), A. parvus LMG 21765(T) A. junii LMG 998(T) and A. soli JCM 15062(T), were found to be less than 8%. The major cellular fatty acids of strain A648(T) were 18:1ω9c (19.6%), summed feature 3 (15.9%), 16:0 (10.6%) and 12:0 (6.4%). The DNA G+C content was 40.4 mol%. The polar lipid profile of strain A648(T) indicated the presence of diphosphatidylglycerol, phosphatidylethanolamine, followed by phosphatidylglycerol and phosphatidylcholine. The predominant polyamine of strain A648(T) was 1,3-diaminopropane and moderate amounts of putrescine, spermidine and spermine were also detected. The respiratory quinone consisted of ubiquinone with nine isoprene units (Q-9). On the basis of DNA-DNA hybridization, phenotypic characteristics and chemotaxonomic and phylogenetic comparisons with other members of the genus Acinetobacter, strain A648(T) is found to be a novel species of the genus Acinetobacter, for which the name Acinetobacter indicus sp. nov. is proposed. The type strain is A648(T) ( = DSM 25388(T) = CCM 7832(T)).

  8. ANALYSIS OF 2,3,7,8-TCDD TUMOR PROMOTION ACTIVITY AND ITS RELATIONSHIP TO CANCER

    Science.gov (United States)

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a high estimated cancer potency in animals which has been reasoned to imply that TCDD might be carcinogenic to man. The animal cancer data show that TCDD can act in a solitary manner causing tumors without the participation of other ...

  9. Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin.

    Science.gov (United States)

    Martyniuk, Christopher J; Doperalski, Nicholas J; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2013-01-01

    Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3mg dieldrin/kg feed in a 2 month feeding exposure (August-October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin neurotoxicity; and (3) determine whether or not co-feeding with 17β-estradiol (E(2)), a hormone with neuroprotective roles, mitigates responses in males to dieldrin. Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints (e.g. gonadosomatic index, vitellogenin, or plasma E(2)). Sub-network (SNEA) and gene set enrichment analysis (GSEA) revealed that neuro-hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure. Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin. These data suggest that (1) there are sexually dimorphic responses in the teleost hypothalamus; (2) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and (3) males co-fed dieldrin and E(2) had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E(2) may mitigate the effects of dieldrin in the central nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Effects of TCDD on thyroid hormone homeostasis in the rat.

    Science.gov (United States)

    Kohn, M C

    2000-02-01

    A physiological dosimetric model was constructed to describe the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on circulating thyroid hormones in the rat and to test the hypothesis that these hormonal changes cause chronically elevated serum thyrotropin (thyroid stimulating hormone, TSH), which mediates growth promotion and may lead to thyroid tumors in TCDD-treated rats. The model included diffusion restricted distribution of TCDD among compartments for liver, kidney, white fat, slowly and rapidly perfused tissues, and the thyroxine-sensitive tissues brown fat, pituitary, and thyroid. Blood was distributed among major vessels and the capillary beds of the tissues. Metabolism of TCDD was limited to the liver. Secretion of 3,5,3'-triiodothyronine (T3) and thyroxine (3,5,3',5'-tetraiodothyronine, T4) from the thyroid was modeled as stimulated by circulating TSH, whose release from the pituitary was regulated by the hypothalamic peptides thyrotropin releasing hormone (activating) and somatostatin (inhibiting). Release of these peptides was represented as inhibited and activated, respectively, by circulating T4. Binding proteins for T3 and T4 and metabolism of the hormones by deiodination were included in thyroxine-sensitive tissues. Induction of hepatic UDP-glucuronosyltransferase-1*6 (UGT), the enzyme which glucuronidates T4, was modeled as induced by the complex formed between TCDD and the aryl hydrocarbon receptor. The computed extent of deiodination, primacy of the thyroid in generating T3 from T4, dependence of liver and kidney on locally produced T3, and export of T3 formed in the pituitary agreed with experimental observations. The model reproduced the observed decrease in circulating T4 and elevated serum TSH following chronic administration of TCDD. The altered levels were attributed to the increased clearance of T4 by the induced UGT and the consequent modification of feedback control of hormone releases. These results are consistent with the

  11. Developmental and lactational exposure to dieldrin alters mammary tumorigenesis in Her2/neu transgenic mice.

    Directory of Open Access Journals (Sweden)

    Heather L Cameron

    Full Text Available Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil, or dieldrin (0.45, 2.25, and 4.5 microg/g body weight daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

  12. Comparative effects of DDT, allethrin, dieldrin and aldrin-transdiol on sense organs of Xenopus laevis

    NARCIS (Netherlands)

    Akkermans, L.M.A.; Bercken, J. van den; Versluijs-Helder, M.

    1975-01-01

    The effects of DDT, allethrin, dieldrin and aldrin-transdiol were studied in two different sense organs of Xenopus laevis; the lateral-line organ and the cutaneous touch receptors. DDT and allethrin produced pronounced repetitive firing in both preparations. Dieldrin and aldrin-transdiol, on the oth

  13. Assessing the phytoavailability of dieldrin residues in charcoal-amended soil using tenax extraction.

    Science.gov (United States)

    Hilber, Isabel; Bucheli, Thomas D; Wyss, Gabriela S; Schulin, Rainer

    2009-05-27

    Consecutive and single Tenax extractions were applied to characterize the effectiveness of activated charcoal (AC) amendments to reduce the phytoavailability of dieldrin in a natively contaminated horticultural soil. Dieldrin desorption from untreated and 800 mg(AC) kg(-1) soil was well described by a model with three dieldrin fractions of different kinetics: a rapidly (F(rap)), slowly (F(slow)), and very slowly (F(v.slow)) desorbing fraction. The AC amendment resulted in a transfer of dieldrin from the F(slow) to the F(v.slow) fraction. The F(v.slow) increased by nearly 10% compared to the control soil. Dieldrin extractability by Tenax from AC amended soils was not influenced by the cultivation of cucumber plants indicating the stability of this remediation technique. Dieldrin extractability by Tenax at the beginning of plant growth correlated only weakly with the dieldrin content of the cucumbers at harvest. Therefore, the potential of Tenax extractions to predict the uptake of dieldrin by cucumbers appears to be limited.

  14. Determination of dieldrin in wool products by gas chromatography with microwave-assisted extraction.

    Science.gov (United States)

    Ohto, Mikiya; Kodama, Shuji; Saito, Yukio; Yamamoto, Atushi

    2006-12-01

    Dieldrin is a moth-proofing agent that was banned by the Stockholm Convention in 2001. The amount of dieldrin in wool products was measured by a microwave-assisted extraction (MAE) method. The optimal conditions were as follows: extraction solvent, acetone/n-hexane (1:1 v/v); extraction temperature, 110 degrees C; extraction time, 10 min; solvent volume, 25 mL. When six samples were used, dieldrin contents determined by GC with the proposed MAE agreed closely with those by the Japanese official method using GC with solvent extraction and cleanup by column chromatography. The proposed MAE has two merits. First, the pretreatment of the MAE needs only 4 h for 11 samples, while that using the Japanese official method needs 2 days for six samples. Second, the volume of organic solvents used for the proposed method was only about one-tenth of that used in the Japanese official method. Our proposed method seems to be easy and useful for daily (routine) tests. Dieldrin contents of 28 used wool products, which were obtained from local clothing shops and ordinary homes, were determined by GC with the proposed MAE, and six products contained dieldrin (0.310-175 ppm). The dry cleaning of the woolen yarn containing 175 ppm dieldrin did not remove a significant amount of dieldrin. Therefore, it seems likely that dieldrin is still distributed slightly but widely throughout the world.

  15. Organochlorine pesticides dieldrin and lindane induce cooperative toxicity in dopaminergic neurons: role of oxidative stress.

    Science.gov (United States)

    Sharma, Heera; Zhang, Ping; Barber, David S; Liu, Bin

    2010-03-01

    Elevated environmental exposure to pesticides has been implicated as a contributing factor in the pathogenesis of Parkinson's disease (PD), a progressive movement disorder resulted from degeneration of the nigrostriatal dopaminergic (DA) pathway. Organochlorine pesticides (OCPs) including dieldrin and lindane remain ubiquitous in the environment and food supply due to their resistance to degradation and bioaccumulation along the food chain. While prior studies have gained insight into the neurotoxic effects of individual OCPs such as dieldrin, the effect of combinations of coexisting OCPs is lacking. In this study, we determined the combined effect of dieldrin and lindane on DA neurons and potential mechanism of action. Combinations of dieldrin and lindane (5-25 microM) were more effective in causing toxicity in immortalized rat N27 DA neurons than when used alone. Mechanistically, dieldrin and lindane combination induced a rapid increase in the levels of intracellular reactive oxygen species, a decrease in mitochondrial membrane potential and activation of caspase 3/7. Pretreatment with antioxidant N-acetyl cysteine blocked the effect of dieldrin and lindane on ROS generation and mitochondrial membrane potential and protected against dieldrin- and lindane-induced neurotoxicity. These results demonstrate that dieldrin and lindane work cooperatively to induce DA neurotoxicity through the induction of oxidative stress and mitochondrial dysfunction. These findings may advance understanding of the role of pesticides in the multi-factorial etiology of PD. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  16. Comparative effects of DDT, allethrin, dieldrin and aldrin-transdiol on sense organs of Xenopus laevis

    NARCIS (Netherlands)

    Akkermans, L.M.A.; Bercken, J. van den; Versluijs-Helder, M.

    1975-01-01

    The effects of DDT, allethrin, dieldrin and aldrin-transdiol were studied in two different sense organs of Xenopus laevis; the lateral-line organ and the cutaneous touch receptors. DDT and allethrin produced pronounced repetitive firing in both preparations. Dieldrin and aldrin-transdiol, on the

  17. Developmental and lactational exposure to dieldrin alters mammary tumorigenesis in Her2/neu transgenic mice.

    Science.gov (United States)

    Cameron, Heather L; Foster, Warren G

    2009-01-01

    Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 microg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

  18. Theoretical Study of the Diastereofacial Isomers of Aldrin and Dieldrin

    Directory of Open Access Journals (Sweden)

    Zoran Zdravkovski

    2006-02-01

    Full Text Available The Diels-Alder reaction of hexachlorocyclopentadiene with norbornadiene givesaldrin but theoretically three other diastereofacial isomers are possible. On oxidation theseisomers can generate eight adducts one of which is known as dieldrin. All these, as well asthe corresponding reactions with hexafluorocyclopenadiene were studied by semiempirical(AM1 and PM3 and hybrid density functional (B3LYP methods. Besides the energy levels,the transition states were calculated for the reactions leading to the diastereofacial isomers ofaldrin, which indicate that aldrin is the favored product of the reaction both fromthermodynamic and kinetic point of view.

  19. Accumulation of dieldrin in an alga (Scenedesmus obliquus), Daphnia magna, and the guppy (Poecilia reticulata)

    Science.gov (United States)

    Reinert, Robert E.

    1972-01-01

    Scenedesmus obliquus, Daphnia magna, and Poecilia reticulata accumulated dieldrin directly from water; average concentration factors (concentration in organism, dry weight, divided by concentration in water) were 1282 for the alga, 13,954 for D. magna, and 49,307 (estimated) for the guppy. The amount accumulated by each species at equilibrium (after about 1.5, 3-4, and 18 days, respectively) was directly proportional to the concentration of dieldrin in the water. Daphnia magna and guppies accumulated more dieldrin from water than from food that had been exposed to similar concentrations in water. When guppies were fed equal daily rations of D. magna containing different concentrations of insecticide, the amounts of dieldrin accumulated by the fish were directly proportional to the concentration in D. magna; when two lots of guppies were fed different quantities of D. magna (10 and 20 organisms per day) containing identical concentrations of dieldrin, however, the amounts accumulated did not differ substantially.

  20. Serum TCDD and TEQ concentrations among Seveso women, 20 years after the explosion.

    Science.gov (United States)

    Warner, Marcella; Mocarelli, Paolo; Brambilla, Paolo; Wesselink, Amelia; Patterson, Don G; Turner, Wayman E; Eskenazi, Brenda

    2014-11-01

    The Seveso Women's Health Study (SWHS) is a historical cohort study of the female population residing near Seveso, Italy, on 10 July 1976, when a chemical explosion resulted in the highest known residential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Individual TCDD concentration was measured in serum collected near the time of the explosion, and in 1996, we collected adequate blood for TCDD and total dioxin toxic equivalent (TEQ) measurement. Polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls were measured in 1996 serum for a sample (n=225, 23%) of the SWHS cohort and WHO 2005 TEQs were calculated. We examined characteristics that predict 1996 TCDD concentrations and estimated TCDD elimination half-life over the 20-year period since the explosion. Median lipid-adjusted TCDD and total TEQ concentrations in 1996 serum were 7.3 and 26.2 p.p.t., respectively. Initial 1976 TCDD and age at explosion were the strongest predictors of 1996 TCDD. The TCDD elimination half-life was 7.1 years for women older than 10 years in 1976, but was shorter in those who were younger. Twenty years after the explosion, TCDD concentrations in this SWHS sample, the majority of who were children in 1976, remain elevated relative to background. These data add to the limited data available on TCDD elimination half-life in children.

  1. Effects of Chronic Dieldrin Ingestion on the Muscular Efficiency of Rats

    Science.gov (United States)

    Khaïry, Mélék

    1960-01-01

    Several cases of dieldrin poisoning were reported amongst sprayers following repeated exposure to this insecticide. The symptoms developed by some of the most severe cases of poisoning included epileptiform convulsions. The effect of dieldrin on muscular efficiency of rats was studied. A state of chronic toxicity was produced by maintaining two groups of rats on a diet containing 25 p.p.m. and 50 p.p.m. of dieldrin respectively. A third group receiving a diet containing no dieldrin acted as a control. Muscular efficiency was measured by training the rats to pull weights of increasing magnitude in a 250 cm. runway. The time taken to pull the weights through the standard distance was recorded. Dieldrin appeared to have no effect on body weight, food intake, or learning, but muscular efficiency (as measured here) seemed to be affected by this compound. A progressive deterioration in muscular efficiency was observed, and was related to the amount of dieldrin administered. Although the nature of the deterioration cannot be deduced from this study, the results obtained here suggest possible lines of investigating the early effects on human beings of exposure to dieldrin. Images PMID:14408763

  2. Dieldrin-dissolving abilities of the xylem saps of several plant families, particularly Cucurbita pepo L.

    Science.gov (United States)

    Murano, Hirotatsu; Otani, Takashi; Seike, Nobuyasu

    2010-10-01

    The uptake ability of hydrophobic organic chemicals by plants and the nature of xylem sap of the plants were studied. The plants were grown in soil contaminated with dieldrin. High amounts of dieldrin were detected in the shoots of Cucurbita pepo and Cucumis sativus, but little was seen in the shoots of Brassica oleracea var. italica, Solanum lycopersicum, Glycine max, Zea mays, and Helianthus annuus. The xylem saps of C. pepo and C. sativus leached dieldrin adsorbed on C8 granules, but those of the other plants did not. The xylem saps of C. pepo and C. sativus eluted high amounts of dieldrin from the size-exclusion chromatography column near the fractions of RNase A (13.7 kDa) after Aprotinin (6.5 kDa), which has a larger molecular weight than dieldrin (381). The enhancement of dieldrin solubility by xylem sap was reduced by proteinase and heating. It was suspected that the protein-like materials in the xylem sap delivered dieldrin from the roots to the shoots. Environ. Toxicol. Chem. 2010;29:2269-2277. © 2010 SETAC.

  3. Bioconversion of dieldrin by wood-rotting fungi and metabolite detection.

    Science.gov (United States)

    Kamei, Ichiro; Takagi, Kazuhiro; Kondo, Ryuichiro

    2010-08-01

    Dieldrin is one of the most persistent organochlorine pesticides, listed as one of the 12 persistent organic pollutants in the Stockholm Convention. Although microbial degradation is an effective way to remediate environmental pollutants, reports on aerobic microbial degradation of dieldrin are limited. Wood-rotting fungi can degrade a wide spectrum of recalcitrant organopollutants, and an attempt has been made to select wood-rotting fungi that can degrade dieldrin, and to identify the metabolite. Thirty-four isolates of wood-rotting fungi were investigated for their ability to degrade dieldrin. Strain YK543 degraded 39.1 +/- 8.8% of dieldrin during 30 days of incubation. Phylogenetic analysis demonstrated that strain YK543 was closely related to the fungus Phlebia brevispora Nakasone TMIC33929, which has been reported as a fungus that can degrade chlorinated dioxins and polychlorinated biphenyls. 9-Hydroxydieldrin was detected as a metabolite in the cultures of strain YK543. It is important to select the microorganisms that degrade organic pollutants, and to identify the metabolic pathway for the development of bioremediation methods. Strain YK543 was selected as a fungus capable of degrading dieldrin. The metabolic pathway includes 9-hydroxylation reported in rat's metabolism catalysed by liver microsomal monooxygenase. This is the first report of transformation of dieldrin to 9-hydroxydieldrin by a microorganism. Copyright (c) 2010 Society of Chemical Industry.

  4. Maternal and cord blood levels of aldrin and dieldrin in Delhi population.

    Science.gov (United States)

    Mustafa, Md; Pathak, Rahul; Tripathi, A K; Ahmed, Rafat S; Guleria, Kiran; Banerjee, B D

    2010-12-01

    Aldrin and dieldrin, structurally similar organochlorine pesticides belong to cyclodiene family and were widely used for agriculture and public health program in India. Although the manufacturing, use and import of aldrin and dieldrin have been banned in India since 2003, these pesticides are still persistent in environment and may be associated with adverse neurological and reproductive effects. The aim of this study is to assess the recent exposure level of aldrin and dieldrin and their placental transfer to fetus in normal healthy full-term pregnant women belonging to north Indian population undergoing normal delivery at Obstetrics and Gynecology department of UCMS and GTB hospital, Delhi. Quantitative analysis of aldrin and dieldrin residues in maternal and cord blood samples were carried out by gas chromatography system equipped with electron capture detector. The results of our study clearly revealed that maternal and cord blood levels of aldrin and dieldrin of pregnant women are age and dietary habit dependent. The aldrin level in maternal blood and dieldrin level in cord blood are higher in women in the age group 25-30 years than in women in age group of 19-24 years. Similarly, aldrin level in maternal blood is significantly higher in women with non-vegetarian dietary habit than in women with vegetarian dietary habit. No significant association is found for maternal and cord blood level. The results of the present study clearly demonstrate prenatal uptake of aldrin and dieldrin and provide recent information on the subsequent transplacental transfer.

  5. Composition of aldrin, dieldrin, and photodieldrin enantiomers in technical and environmental samples.

    Science.gov (United States)

    Buser, Hans-Rudolf; Müller, Markus D; Buerge, Ignaz J; Poiger, Thomas

    2009-08-26

    Aldrin and dieldrin belong to the group of polycyclic chlorinated insecticides that are banned under the Stockholm Convention (POP Convention). Despite the fact that the use of these compounds ceased many years ago, aldrin and, in particular, dieldrin are still present in the environment from former applications, leading occasionally to contamination of agricultural produce and food, particularly Cucurbitaceae. These prochiral compounds have a complex stereochemistry. In the environment, aldrin is rapidly converted to its epoxide, dieldrin. Photolysis is one of the environmental transformation processes reported to be important for the compounds, leading to photoproducts such as photoaldrin and photodieldrin. In contrast to the parent compounds, photoaldrin and photodieldrin are chiral and exist as pairs of enantiomers. Although dieldrin and its metabolites have been extensively reviewed, the chirality of many of its metabolites has so far not been considered. In this study, the composition of technical aldrin and dieldrin from the 1950s and their photoproducts was investigated using both non-enantioselective and enantioselective gas chromatography with detection by several mass spectrometric techniques. Full enantiomer resolution of photodieldrin was achieved using a column with a silylated gamma-cyclodextrin as chiral selector. Photoaldrin, however, showed peak broadening, indicating some marginal resolution of the enantiomers. Whereas photodieldrin was formed as a racemate from both aldrin and dieldrin by natural sunlight, the analysis of environmental and biological samples (soil, biota) indicated its presence mostly with enantiomer compositions clearly differing from 1:1. The presence of photodieldrin in soil, treated more than 40 years ago with aldrin or dieldrin, documents that the photoreaction of dieldrin plays some role in the transformation of the compounds in the environment and that enantioselective biological processes are involved in its further

  6. Differential actions of fipronil and dieldrin insecticides on GABA-gated chloride channels in cockroach neurons.

    Science.gov (United States)

    Zhao, Xilong; Salgado, Vincent L; Yeh, Jay Z; Narahashi, Toshio

    2003-09-01

    Fipronil and dieldrin are known to inhibit GABA receptors in both mammals and insects. However, the mechanism of selective toxicity of these insecticides between mammals and insects remains to be seen. One possible mechanism is that insect GABA receptors are more sensitive than mammalian GABAA receptors to fipronil and dieldrin. We examined differential actions of fipronil and dieldrin on GABA-gated chloride channels in insects and compared them with the data on mammalian GABAA receptors. Neurons were acutely dissociated from the American cockroach thoracic ganglia, and currents evoked by GABA were recorded by the whole-cell patch-clamp technique. GABA-evoked currents were carried by chloride ions, blocked by picrotoxinin, but not by bicuculline. Fipronil inhibited GABA currents with an IC50 value of 28 nM, whereas dieldrin exhibited a dual action potentiation with an EC50 value of 4 nM followed by inhibition with an IC50 value of 16 nM. Fipronil and dieldrin acted on the resting receptor at comparable rates, whereas fipronil blocked the activated receptor 10 times faster than dieldrin. Fipronil inhibition was partially reversible, whereas dieldrin inhibition was irreversible. Fipronil was 59 times more potent on cockroach GABA receptors than on rat GABAA receptors. However, the potentiating and inhibitory potencies of dieldrin in cockroach GABA receptors were comparable with those in rat GABAA receptors. It was concluded that the higher toxicity of fipronil in insects than in mammals is due partially to the higher sensitivity of GABA receptors. The mechanism of dieldrin's selective toxicity must lie in factors other than the sensitivity of GABA receptors.

  7. Induction of microglial reactive oxygen species production by the organochlorinated pesticide dieldrin.

    Science.gov (United States)

    Mao, Haoyu; Fang, Xi; Floyd, Katon M; Polcz, Jeanette E; Zhang, Ping; Liu, Bin

    2007-12-01

    Exposure to pesticides has been speculated to contribute to the development of sporadic Parkinson's disease (PD) characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway. Activation of brain microglia that produce various neurotoxic factors including cytokines and reactive oxygen species (ROS) has been increasingly associated with dopaminergic neurodegeneration induced by various toxicants. Dieldrin, a highly persistent organochlorinated pesticide found enriched in the substantia nigra of some postmortem PD brains, has been shown to be toxic to dopamine neurons. In this study, we set out to determine the effect of dieldrin on the production of ROS and the underlying mechanism of action in murine microglia. Treatment of microglial cells with 0.1 nM to 1 microM dieldrin for 24 h resulted in a concentration-dependent generation of ROS. The dieldrin-induced microglial ROS generation was time-dependent in that significant ROS production was observed in cells 12-24 h, but not 6 h after dieldrin treatment. Furthermore, the dieldrin-induced microglial ROS generation was significantly reduced by inhibitors of NADPH oxidase, gene transcription and protein synthesis. In addition to immortalized microglial cells, dieldrin induced a concentration-dependent ROS generation in primary microglia, but not in primary astroglia. These results demonstrate that nanomolar concentrations of dieldrin can stimulate microglia to produce ROS that may contribute to the degeneration of dopamine neurons known to be vulnerable to oxidative damage. These findings provide important information on the potential role of microglia in dieldrin-induced neurodegeneration in relevance to the development of idiopathic PD.

  8. Bioremediation of the organochlorine pesticides, dieldrin and endrin, and their occurrence in the environment.

    Science.gov (United States)

    Matsumoto, Emiko; Kawanaka, Youhei; Yun, Sun-Ja; Oyaizu, Hiroshi

    2009-08-01

    Dieldrin and endrin are persistent organic pollutants that cause serious environmental problems. Although these compounds have been prohibited over the past decades in most countries around the world, they are still routinely found in the environment, especially in the soil in agricultural fields. Bioremediation, including phytoremediation and rhizoremediation, is expected to be a useful cleanup method for this soil contamination. This review provides an overview of the environmental contamination by dieldrin and endrin, along with a summary of our current understanding and recent advances in bioremediation and phytoremediation of these pollutants. In particular, this review focuses on the types and abilities of plants and microorganisms available for accumulating and degrading dieldrin and endrin.

  9. The effects of dieldrin on various life stages of the African catfish Clarias gariepinus (Burchell)

    OpenAIRE

    Lamai, S.L.; Walker, C. H.; Warner, G. F.

    2001-01-01

    Early life stages (ELS) of Clarias gariepinus were found to be less sensitive to acute dieldrin toxicity than ELS of Nile tilapia, Oreochromis niloticus; 96 h LC50 for 37 day old fry were 11.7 and 4.95pg/l, respectively. Growth of O. niloticus fry was significantly reduced in 22.4 pg/l dieldrin whereas growth of C. gariepinus fry was unaffected. Adult C. gariepinus rapidly absorbed dieldrin from aquaeous solution and accumulated it in their tissues, especially in the liver where after 30 days...

  10. Concentrations of DDTs and dieldrin in Long Island Sound sediment.

    Science.gov (United States)

    Yang, Lijia; Li, Xiqing; Zhang, Pengfei; Melcer, Michael E; Wu, Youxian; Jans, Urs

    2012-03-01

    The concentrations of three frequently detected organochlorine pesticides (OCPs) and one degradation product, p,p'-DDT, p,p'-DDD, dieldrin, and p,p'-DDE were determined in recently collected (2005-2006) and archived (1986-1989) surficial sediments and sediment cores from Long Island Sound (LIS). The concentration of dieldrin ranged from 0.05 to 5.27 ng g(-1) dry weight in the surficial sediments, and from 0.05 to 11.7 ng g(-1) dry weight in the sediment cores. Total DDXs (the sum of p,p'-DDE, p,p'-DDD and p,p'-DDT) concentrations ranged from 1.31 to 33.2 ng g(-1) in surficial sediments and 1.11 to 66.4 ng g(-1) in sediment cores. The results indicate that the three OCPs and DDE were still widely present in LIS surficial sediments two decades after the use of these pesticides in the United States was banned. In addition, the surficial concentrations did not decrease significantly when compared to the concentrations in archived samples collected two decades ago. Sediments in the western part of LIS were more contaminated (with concentrations in some western sites being still above probable effect levels) than those in the eastern part, probably as a result of the net westward sediment transport in LIS. The three OCPs and DDE were detected at all depths (down to ~50 cm) in the sediment cores, and concentration profiles indicated a depositional sedimentary environment with significant sediment mixing. Such mixing may redistribute OCPs deposited earlier (deeper in sediment bed) to the sediment surface and lead to enhanced persistence of OCP concentrations in surficial sediments. This journal is © The Royal Society of Chemistry 2012

  11. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hormones of energy balance in a TCDD-sensitive and a TCDD-resistant rat strain.

    Science.gov (United States)

    Lindén, Jere; Lensu, Sanna; Pohjanvirta, Raimo

    2014-08-12

    One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21), appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance.

  12. Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain

    Directory of Open Access Journals (Sweden)

    Jere Lindén

    2014-08-01

    Full Text Available One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21, appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance.

  13. Protective effects of quercetin on dieldrin-induced endoplasmic reticulum stress and apoptosis in dopaminergic neuronal cells.

    Science.gov (United States)

    Park, Euteum; Chun, Hong Sung

    2016-10-19

    Dieldrin, an organochlorine pesticide still used in several developing countries, has been proposed as a risk factor for Parkinson's disease. Quercetin is one of the potent bioactive flavonoids present in numerous plants. In this study, we investigated the protective effects of quercetin on neurotoxicity induced by dieldrin in cultured dopaminergic SN4741 cells. Our initial experiments showed that quercetin (10-40 μM) dose dependently prevented dieldrin (20 μM)-induced cytotoxicity in SN4741 cells. Pretreatment for 1 h with quercetin before dieldrin application could significantly suppress dieldrin-induced apoptotic characteristics, including nuclear condensation, DNA fragmentation, and caspase-3/7 activation. Results showed that dieldrin-induced markers of endoplasmic reticulum (ER) stress response such as chaperone GRP78, heme oxygenase-1, and phosphorylation of the α subunit of eukaryotic initiation factor 2. In addition, dieldrin reduced antiapoptotic Bcl-2 expression, but significantly elevated a proapoptotic transcription factor CHOP. Furthermore, RNA interference to CHOP almost completely repressed dieldrin-induced apoptotic cell death. Interestingly, quercetin prevented the changes in dieldrin-induced ER stress markers. These results suggest that quercetin may suppress the ER stress-CHOP pathway and dieldrin-induced apoptosis in dopaminergic neurons.

  14. Isolation of dieldrin- and endrin-degrading bacteria using 1,2-epoxycyclohexane as a structural analog of both compounds.

    Science.gov (United States)

    Matsumoto, Emiko; Kawanaka, Youhei; Yun, Sun-Ja; Oyaizu, Hiroshi

    2008-10-01

    This report describes the selective isolation of dieldrin- and endrin-degrading bacteria from soil with high degradation activity toward dieldrin and endrin. Several enrichment cultures from the soil were arranged with several structural analogs of dieldrin and endrin as a growth substrate and examined for their degradation activities toward dieldrin and endrin. An enrichment culture with 1,2-epoxycyclohexane (ECH) was found to aerobically degrade dieldrin and endrin. Denaturing gradient gel electrophoresis (DGGE) indicated that three types of bacteria were predominant in the ECH enrichment culture. Of the three major bacteria, two isolates, Burkholderia sp. strain MED-7 and Cupriavidus sp. strain MED-5, showed high degradation activity toward dieldrin and endrin. The degradation efficiencies of strain MED-7 and MED-5 were 49% and 38% toward dieldrin, respectively, and 51% and 40% toward endrin, respectively, in the presence of ECH for 14 days. These results indicated that ECH was a useful substrate for selective and efficient isolation of dieldrin- and endrin-degrading bacteria from soil containing numerous bacteria. Interestingly, the two isolates could also degrade dieldrin and endrin even in the absence of ECH. These are the first microorganisms demonstrated to grow on dieldrin and endrin as the sole carbon and energy source under aerobic conditions.

  15. Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.

    Science.gov (United States)

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2014-09-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish.

  16. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) enhances placental inflammation

    OpenAIRE

    Peltier, Morgan R; Arita, Yuko; Klimova, Natalia G.; Gurzenda, Ellen M.; Koo, Hchi-Chi; Murthy, Amitasrigowri; Lerner, Veronica; Hanna, Nazeeh

    2013-01-01

    Preterm birth is a leading cause of perinatal morbidity and mortality that is often associated with ascending infections from the lower genital tract. Recent studies with animal models have suggested that developmental exposure to the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can increase the risk of preterm birth in the offspring. How TCDD may modify placental immunity to ascending infections is unclear. Therefore, we studied the effects of TCDD treatment on basal and Es...

  17. Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain

    OpenAIRE

    2014-01-01

    One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 da...

  18. Report of aldrin, dieldrin, endrin, and mercury analysis : Rocky Mountain Arsenal project

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Contaminant study at the Rocky Mountain Arsenal to determine the levels of aldrin, dieldrin, endrin, and mercury in various sample substrates as well as background...

  19. FISH TISSUE RESIDUE-BASED WILDLIFE VALUES FOR PISCIVOUOUS WILDLIFE: CHLORDANE, DDT, DIELDRIN, HEXACHLOROBENZENE

    Science.gov (United States)

    Fish tissue residue-based wildlife values were derived for chlordane, DDT, dieldrin, endrin, hexachlorobenzene, mercury and PCBs. Piscivorous wildlife for which these benchmarks were derived include belted kingfisher, river otter and mink. Toxic endpoint selection, criteria for t...

  20. PROCEDURES FOR DERIVING EQUILIBRIUM PARTITIONING SEDIMENT BENCHMARKS (ESBS) FOR THE PROTECTION OF BENTHIC ORGANISMS: DIELDRIN

    Science.gov (United States)

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations of the insecticide dieldrin in sediment which are protective of the presence of benthic organisms. The equilibrium partitioning (EqP) approach was chosen because it acco...

  1. Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/neu Transgenic Mice

    OpenAIRE

    Cameron, Heather L.; Foster, Warren G.

    2009-01-01

    Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offsprin...

  2. ANALYSIS OF 2,3,7,8-TCDD TUMOR PROMOTION ACTIVITY ...

    Science.gov (United States)

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a high estimated cancer potency in animals which has been reasoned to imply that TCDD might be carcinogenic to man. The animal cancer data show that TCDD can act in a solitary manner causing tumors without the participation of other known factors. owever, there exist animal cancer data indicating that TCDD can act as a tumor-promoting compound. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites. These observations in toto characterize TCDD as a complete carcinogen, which by definition encompasses both initiation and promotion carcinogenic activities. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites

  3. Reversible activation of the neutrophil superoxide generating system by hexachlorocyclohexane: correlation with effects on a subcellular superoxide-generating fraction

    Energy Technology Data Exchange (ETDEWEB)

    English, D.; Schell, M.; Siakotos, A.; Gabig, T.G.

    1986-07-01

    ..gamma..-hexachlorocyclohexane was found to exert profound effects on the phosphatidylinositol cycle, cytosolic calcium level, and the respiratory burst of human neutrophils. Exposure of neutrophils prelabelled with /sup 32/P to 4 x 10/sup -4/ M ..gamma..-hexachlorocyclohexane almost tripled radioactivity in phosphatidic acid and correspondingly decreased radioactivity in phosphatidylinositol 4,5 bisphosphate. Under similar conditions, ..gamma..-hexachlorocyclohexane evoked the generation of superoxide at a rate of over 11 nmol/min/10/sup 6/ cells and more than doubled cytosolic-free calcium concentration as monitored by Quin-2 fluorescence. Because intermediates of the phosphatidylinositol cycle, via increases in available calcium levels or activated protein kinase C, are considered potential second messenger for activation of the NADPH-dependent O/sub 2//sup -/-generating system, neutrophil responses to ..gamma..-hexachlorocyclohexane were compared with responses to phorbol myristate acetate, an activator of protein kinase C with well known effects on neutrophils. Like phorbol myristate acetate, ..gamma..-hexachlorocyclohexane induced neutrophil degranulation but was not an effective chemotactic stimulus. The ability of ..gamma..-hexachlorocyclohexane to induce a pattern of oxidative activation in neutrophil cytoplasts similar to that n intact cells indicated that concurrent degranulation was not required for sustained O/sub 2//sup -/ generation in response to this agent.

  4. Biodegradation of Aldrin and Dieldrin by the White-Rot Fungus Pleurotus ostreatus.

    Science.gov (United States)

    Purnomo, Adi Setyo; Nawfa, Refdinal; Martak, Fahimah; Shimizu, Kuniyoshi; Kamei, Ichiro

    2017-03-01

    Aldrin and its metabolite dieldrin are persistent organic pollutants that contaminate soil in many parts of the world. Given the potential hazards associated with these pollutants, an efficient degradation method is required. In this study, we investigated the ability of Pleurotus ostreatus to transform aldrin as well as dieldrin in pure liquid cultures. This fungus completely eliminated aldrin in potato dextrose broth (PDB) medium during a 14-day incubation period. Dieldrin was detected as the main metabolite, and 9-hydroxylaldrin and 9-hydroxyldieldrin were less abundant metabolites. The proposed route of aldrin biotransformation is initial metabolism by epoxidation, followed by hydroxylation. The fungus was also capable of degrading dieldrin, a recalcitrant metabolite of aldrin. Approximately 3, 9, and 18% of dieldrin were eliminated by P. ostreatus in low-nitrogen, high-nitrogen, and PDB media, respectively, during a 14-day incubation period. 9-Dihydroxydieldrin was detected as a metabolite in the PDB culture, suggesting that the hydroxylation reaction occurred in the epoxide ring. These results indicate that P. ostreatus has potential applications in the transformation of aldrin as well as dieldrin.

  5. Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up.

    Science.gov (United States)

    van Amelsvoort, Ludovic G P M; Slangen, Jos J M; Tsai, Shan P; de Jong, Geert; Kant, Ijmert

    2009-01-01

    Dieldrin and aldrin, pesticides widely used until the 1970s, have been under suspicion of being carcinogenic. In this study, overall and cause-specific mortality was assessed in a cohort of 570 employees occupationally exposed to the pesticides dieldrin and aldrin to investigate the long-term health effects, in particular carcinogenic effects. All of the employees worked in the production plants between January 1954 and January 1970 and were followed for cause-specific mortality until 30 April 2006. Based on dieldrin levels in blood samples taken from 343 workers during the exposure period, the total intake of dieldrin was estimated for each individual subjects in the cohort. The estimated total intake ranged from 11 to 7,755 mg of dieldrin, with an average of 737 mg. Two hundred and twenty-six workers had died before 30 April 2006 compared with an expected number of 327.3, giving a standardized mortality ratio (SMR) of 69.0 (95% confidence interval (CI): 60.3-78.7). Overall cancer mortality was also significantly lower than expected (SMR: 76.4, 95% CI: 60.8-94.9). Also, none of the specific cancer sites showed a significant excess mortality and no association between exposure level and cancer mortality was found. The results from this study support findings from other epidemiological and recent animal studies concluding that dieldrin and aldrin are not likely human carcinogens.

  6. Genomic and proteomic responses to environmentally relevant exposures to dieldrin: indicators of neurodegeneration?

    Science.gov (United States)

    Martyniuk, Christopher J; Kroll, Kevin J; Doperalski, Nicholas J; Barber, David S; Denslow, Nancy D

    2010-09-01

    Dieldrin is a persistent organochlorine pesticide that induces neurotoxicity in the vertebrate central nervous system and impairs reproductive processes in fish. This study examined the molecular events produced by subchronic dietary exposures to 2.95 mg dieldrin/kg feed in the neuroendocrine brain of largemouth bass, an apex predator. Microarrays, proteomics, and pathway analysis were performed to identify genes, proteins, and cell processes altered in the male hypothalamus. Fifty-four genes were induced, and 220 genes were reduced in steady-state levels (p dieldrin. Using isobaric tagging for relative and absolute quantitation, 90 proteins in the male hypothalamus were statistically evaluated for changes in protein abundance. Several proteins altered by dieldrin are known to be associated with human neurodegenerative diseases, including apolipoprotein E, microtubule-associated tau protein, enolase 1, stathmin 1a, myelin basic protein, and parvalbumin. Proteins altered by dieldrin were involved in oxidative phosphorylation, differentiation, proliferation, and cell survival. This study demonstrates that a subchronic exposure to dieldrin alters the abundance of messenger RNAs and proteins in the hypothalamus that are associated with cell metabolism, cell stability and integrity, stress, and DNA repair.

  7. Dieldrin elicits a widespread DNA repair and antioxidative response in mouse brain.

    Science.gov (United States)

    Sava, Vasyl; Velasquez, Adriana; Song, Shijie; Sanchez-Ramos, Juan

    2007-01-01

    Dieldrin is an organochlorine pesticide that is toxic for monoaminergic neurons. This study was designed to test the hypothesis that a weak DNA repair response to dieldrin by nigrostriatal dopaminergic (DA) neurons results in depletion of striatal DA. The activity of the mammalian base excision repair enzyme oxyguanosine glycosylase was utilized as the index of DNA repair. Other measures of oxidative stress were also studied, including the regional distribution of lipid peroxidation and superoxide dismutase (SOD) activity. The effects of acute and slow infusion of dieldrin on striatal DA levels were biphasic with a transient initial depression followed by increases beyond normal steady-:state levels. Dieldrin administration caused a global oxidative stress evidenced by increased levels of lipid peroxidation in all brain regions, an effect consistent with its capacity to affect mitochondrial bioenergetics. Dieldrin also elicited strong antioxidative and DNA repair responses across the entire mouse brain. Although mitochondrial SOD was not as increased in midbrain as it was in other regions following a cumulative dose of 24 mg/kg, this response, along with the robust DNA repair response, appeared to be sufficient to protect potentially vulnerable DA neurons from cytotoxicity. However, the long-:term consequences of chronic low-:dose dieldrin exposure remain to be studied, especially in light of the concept of "slow excitotoxicity,'' which postulates that even a mild bioenergetic compromise can over time result in the demise of neurons.

  8. Dieldrin promotes resistance to anoikis in breast cancer cells in vitro.

    Science.gov (United States)

    Cameron, Heather L; Foster, Warren G

    2008-02-01

    Epidemiological evidence suggests that exposure to the pesticide dieldrin, is associated with increased risk of breast cancer and mortality. We hypothesize that dieldrin promotes breast cancer by increasing survival of breast cancer cells. The aims of this study were to measure the effect of dieldrin on survival of breast cancer cells and the expression of tyrosine kinase B (TrkB), a suppressor of anoikis (apoptosis triggered by inappropriate anchorage). The human breast cancer cell line MDA-MB-231 was treated with dieldrin and proliferation, viability and resistance to anoikis were measured. TrkB expression was measured by Western blot in lysates and by immunohistochemistry in human tissue specimens. Dieldrin increased resistance to anoikis and TrkB expression. TrkB was expressed in a subset of high-grade breast carcinoma specimens. Our results demonstrate that dieldrin increases resistance to anoikis and expression of TrkB and show for the first time TrkB protein expression in human breast cancer.

  9. Draft Genome Sequence of Sphingobium ummariense Strain RL-3, a Hexachlorocyclohexane-Degrading Bacterium.

    Science.gov (United States)

    Kohli, Puneet; Dua, Ankita; Sangwan, Naseer; Oldach, Phoebe; Khurana, J P; Lal, Rup

    2013-11-14

    Here, we report the draft genome sequence of the hexachlorocyclohexane (HCH)-degrading bacterium Sphingobium ummariense strain RL-3, which was isolated from the HCH dumpsite located in Lucknow, India (27°00'N and 81°09'E). The annotated draft genome sequence (4.75 Mb) of strain RL-3 consisted of 139 contigs, 4,645 coding sequences, and 65% G+C content.

  10. Reversible activation of the neutrophil superoxide generating system by hexachlorocyclohexane: correlation with effects on a subcellular superoxide-generating fraction.

    Science.gov (United States)

    English, D; Schell, M; Siakotos, A; Gabig, T G

    1986-07-01

    gamma-Hexachlorocyclohexane was found to exert profound effects on the phosphatidylinositol cycle, cytosolic calcium level, and the respiratory burst of human neutrophils. Exposure of neutrophils prelabelled with 32P to 4 X 10(-4) M gamma-hexachlorocyclohexane almost tripled radioactivity in phosphatidic acid and correspondingly decreased radioactivity in phosphatidylinositol 4,5 bisphosphate. Under similar conditions, gamma-hexachlorocyclohexane evoked the generation of superoxide at a rate of over 11 nmol/min/10(6) cells and more than doubled cytosolic-free calcium concentration as monitored by Quin-2 fluorescence. Because intermediates of the phosphatidylinositol cycle, via increases in available calcium levels or activated protein kinase C, are considered potential second messengers for activation of the NADPH-dependent O-2-generating system, we compared neutrophil responses to gamma-hexachlorocyclohexane with responses to phorbol myristate acetate, an activator of protein kinase C with well known effects on neutrophils. Like phorbol myristate acetate, gamma-hexachlorocyclohexane induced neutrophil degranulation but was not an effective chemotactic stimulus. The ability of gamma-hexachlorocyclohexane to induce a pattern of oxidative activation in neutrophil cytoplasts similar to that in intact cells indicated that concurrent degranulation was not required for sustained O-2 generation in response to this agent. When neutrophils or neutrophil cytoplasts exposed to gamma-hexachlorocyclohexane were centrifuged and resuspended in stimulus-free medium, O-2 generation ceased entirely but could be reinitiated by addition of the same stimulus. This finding was in contrast to the continued O-2 production by phorbol myristate acetate-stimulated neutrophils similarly washed and resuspended in stimulus-free medium. Unlike subcellular fractions of phorbol myristate acetate-stimulated neutrophils, corresponding fractions prepared from gamma-hexachlorocyclohexane

  11. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure.

    Science.gov (United States)

    Liu, Qing; Rise, Matthew L; Spitsbergen, Jan M; Hori, Tiago S; Mieritz, Mark; Geis, Steven; McGraw, Joseph E; Goetz, Giles; Larson, Jeremy; Hutz, Reinhold J; Carvan, Michael J

    2013-09-15

    The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ngTCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ngTCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down-regulated gene among each group based on microarray data, and their QPCR validations are consistent with microarray data for the 10 and 100 ppb TCDD treatment groups after 28 days exposure (pppb group at 28 days, expression of complement component C3-1 and trypsin-1 precursor have a more than 10-fold induction from the microarray experiments, and their QPCR

  12. Luteolin suppresses TCDD-induced wasting syndrome in a cultured adipocyte model.

    Science.gov (United States)

    Ashida, Hitoshi; Harada, Kiyonari; Mishima, Sakiho; Mitani, Takakazu; Yamashita, Yoko; Matsumura, Fumio

    2015-05-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various toxic effects, including wasting syndrome, through activation of an aryl hydrocarbon receptor (AhR). Our previous report demonstrated that certain flavonoids inhibit the activation of AhR and suppress its DNA binding activity. In this study, we searched for an active compound among 13 flavonoids that suppressed TCDD-induced loss of lipid accumulation using 3T3-L1 adipocytes as a cell culture model for wasting syndrome. Two flavonoids, luteolin and epigallocatechin gallate, suppressed TCDD-induced loss of lipid accumulation in this model. We further investigated luteolin to clarify the underlying molecular mechanism and confirmed that luteolin inhibited nuclear translocation of AhR caused by TCDD. Luteolin also inhibited the TCDD-driven decrease in protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Although TCDD alone did not change protein expression of C/EBPβ and C/EBPδ, luteolin and TCDD up-regulated C/EBPδ expression in a dose-dependent manner. On the other hand, TCDD significantly decreased DNA binding of C/EBPβ and C/EBPδ, and luteolin completely canceled TCDD-decreased DNA binding of them. We conclude that luteolin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by preventing a decrease in protein expression of PPARγ and C/EBPα, the master regulators of adipocyte differentiation and in DNA binding of C/EBPβ and C/EBPδ. Moreover, luteolin was rapidly incorporated and accumulated in 3T3-L1 adipocytes. Thus, luteolin is an attractive compound for the prevention of TCDD-induced wasting syndrome.

  13. In vitro cytotoxicity of TCDD on SPC-A1 cells.

    Science.gov (United States)

    Liu, Yan-Qun; Zhou, Yi-Kai

    2006-02-01

    The toxicology of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has been studied mainly with regard to the carcinogenicity of its metabolites, but its phototoxicity is not well understood. Although some studies have indicated the lethal phototoxicity of TCDD, this study was designed to investigate its effect on SPC-A1 cells. SPC-A1 cells were cultured in 1640 medium and treated with 10 nmol/L, 0.1 micromol/L, 1 micromol/L TCDD for either 24 h or 96 h at each concentration. SPC-A1 cells were co-cultured with TCDD at different concentrations. Then the cell morphology, DNA fragment electrophoresis, and cell cycle were analyzed by flow cytometry, and enzyme assays were used to observe the effect of TCDD on the morphology, growth rate, and enxyme change of SPC-A1 cells. With the increasing concentrations of TCDD and prolongation of culture time, the morphology of SPC-A1 cells was changed from round shape to spindle, and the ability of SPC-A1 cells to adhere to wall was decreased. With debris emitted around the cells, the morphologic changes included reduction in cell volume. Nuclear chromatin condensation and PI were observed. With the increasing concentrations of TCDD, DNA ladder occurred. After treatment with TCDD, extraction of cancer cells exhibited typical DNA fragmentation, and flow cytometry analysis showed apoptosis in a dose-dependent manner. As the concentration of TCDD rose from 10 nmol/L to 1 micromol/L, the ratio of apoptotic cells increased from 10.76% to 21.82%. TCDD has in vitro cytotoxicity on SPC-A1 cells, and the cytotoxicity is positively related to its concentration and culture time. TCDD may inhibit the growth and proliferation of SPC-A1 cells through the pathway of apoptosis introduction.

  14. Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

    OpenAIRE

    Martyniuk, Christopher J.; Feswick, April; Spade, Daniel J.; Kroll, Kevin J.; Barber, David S.; Denslow, Nancy D.

    2010-01-01

    Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female la...

  15. Genetic sex separation of the malaria vector, Anopheles arabiensis, by exposing eggs to dieldrin.

    Science.gov (United States)

    Yamada, Hanano; Benedict, Mark Q; Malcolm, Colin A; Oliva, Clelia F; Soliban, Sharon M; Gilles, Jeremie R L

    2012-06-19

    The sterile insect technique (SIT) has been used with success for suppressing or eliminating important insect pests of agricultural or veterinary importance. In order to develop SIT for mosquitoes, female elimination prior to release is essential as they are the disease-transmitting sex. A genetic sexing strain (GSS) of Anopheles arabiensis was created based on resistance to dieldrin, and methods of sex separation at the egg stage were developed. The use of this strain for SIT will require sexually sterile males: useful radiation doses for this purpose were determined for pupae and adults. For the creation of the sexing strain, dieldrin-resistant males were irradiated with 40 Gy using a 60Co source and were subsequently crossed to homozygous susceptible virgin females. Individual families were screened for semi-sterility and for male resistance to dieldrin. For sex separation, eggs of a resulting GSS, ANO IPCL1, were exposed to varying concentrations of dieldrin for different durations. Percent hatch, larval survival, and male and female emergence were recorded. Radiation induced sterility was determined following adult and pupa exposure to gamma rays at 0-105 Gy. Mortality induced by dieldrin treatment, and levels of sterility post radiation were investigated. ANO IPCL1 contains a complex chromosome aberration that pseudo-links the male-determining Y chromosome and dieldrin resistance, conferring high natural semi-sterility. Exposure of eggs to 2, 3, and 4 ppm dieldrin solutions resulted in complete female elimination without a significant decrease of male emergence compared to the controls. A dose of 75 Gy reduced the fertility to 3.8 and 6.9% when males were irradiated as pupae or adults respectively, but the proportions of progeny of these males reaching adulthood were 0.6 and 1.5% respectively The GSS ANO IPCL1 was shown to be a suitable strain for further testing for SIT though high semi-sterility is a disadvantage for mass rearing.

  16. EVIDENCE FOR EGFR PATHWAY MEDIATION OF CLEFT PALATE INDUCTION BY TCDD

    Science.gov (United States)

    EVIDENCE FOR EGFR PATHWAY MEDIATION OF CLEFT PALATE INDUCTION BY TCDD. B D Abbott, A R Buckalew, and K E Leffler. RTD, NHEERL, ORD,US EPA, RTP, NC, USA.2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in C57BL/6J mice, producing cleft palate (CP) after exposure...

  17. Histopathologic alterations associated with global gene expression due to chronic dietary TCDD exposure in juvenile zebrafish.

    Science.gov (United States)

    Liu, Qing; Spitsbergen, Jan M; Cariou, Ronan; Huang, Chun-Yuan; Jiang, Nan; Goetz, Giles; Hutz, Reinhold J; Tonellato, Peter J; Carvan, Michael J

    2014-01-01

    The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb) and male (18.04 ppb) fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption.

  18. Correlation between TCDD acute toxicity and aryl hydrocarbon receptor structure for different mammals.

    Science.gov (United States)

    Wang, Yonghua; Wang, Qiuying; Wu, Bing; Li, Yi; Lu, Guanghua

    2013-03-01

    The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity has large species differences, and TCDD exerts its toxicity by binding into aryl hydrocarbon receptor (AHR). In this study, we applied bioinformatics approaches to quantitatively analyze the correlation between TCDD acute toxicity and AHRs. Seven mammalian AHRs were chosen as target receptors. Low conserved functional domains of AHRs were identified and quantitatively characterized. Linear regression was applied to determine the relationships of different mammalian AHRs and TCDD LD(50) values. The results indicated that ligand binding domain and glutamine-rich domain of mammalian AHRs showed a low degree of conservation. Based on previous literatures, the number of glutamine residues (NOQ) and binding free energy with TCDD were applied to quantitatively represent the differences of glutamine-rich domain and ligand binding domain, respectively. Then, regression equations between studied mammalian AHR structures and TCDD LD(50) were constructed, and high linear correlation was found (R(2)=0.986). This study indicated that mammalian differences of TCDD acute toxicity might be partly determined by the differences of glutamine-rich domain and ligand binding domain of AHR, which provides a potential insight to analyze the species differences of TCDD toxicity.

  19. Obesity and perinatal TCDD exposure increases mammary tumors in FVB mice

    Science.gov (United States)

    Risk of breast cancer has been consistently shown to correlate to total lifetime exposure to estrogens. Because both TCDD exposure and the state of obesity interact with the estrogen pathway, we wanted to investigate how TCDD and obesity interact with mammary cancer susceptibili...

  20. Obesity and perinatal TCDD exposure increases mammary tumor incidence in FVB mice

    Science.gov (United States)

    Breast cancer risk consistently correlates with total lifetime exposure to estrogens. Because both TCDD and adipocytes impact the estrogen pathway, we examined how TCDD and obesity interact to alter mammary cancer susceptibility. At 12.5 days post conception, we exposed FVB fema...

  1. Histopathologic alterations associated with global gene expression due to chronic dietary TCDD exposure in juvenile zebrafish.

    Directory of Open Access Journals (Sweden)

    Qing Liu

    Full Text Available The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb and male (18.04 ppb fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption.

  2. TCDD/TCDF levels in bioaccumulation test tissues and their corresponding sediments

    Energy Technology Data Exchange (ETDEWEB)

    Schrock, M.E. [Battelle Memorial Inst., Columbus, OH (United States); Barrows, E.S. [Battelle/Marine Sciences Lab., Sequim, WA (United States); Rosman, L.B. [Army Corps of Engineers, New York, NY (United States)

    1995-12-31

    Sediments from eight highly urbanized, industrial areas were analyzed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8 tetrachlorodibenzofuran (TCDD/TCDF) contamination. The polychaete Nereis virens was exposed to the contaminated sediment for 28 days and then analyzed for TCDD/TCDF to evaluate the potential bioaccumulation of these contaminants, Levels of TCDD/TCDF accumulated in N. virens in general increased as the amount of sediment contamination increased and were significantly greater than levels in N. virens exposed to uncontaminated sediment. In addition, accumulation factors were calculated based on the levels of TCDD/TCDF in the test organisms and sediments, the organism lipid content, and the sediment total organic carbon content to predict the maximum amount of TCDD/TCDF likely to be accumulated from the sediments.

  3. Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: Insights into TCDD-induced endocrine disruption and reproductive toxicity

    OpenAIRE

    2007-01-01

    TCDD is a reproductive toxicant and endocrine disruptor, yet the mechanisms by which it causes these reproductive alterations are not fully understood. In order to provide additional insight into the molecular mechanisms that underlie TCDD’s reproductive toxicity, we assessed TCDD-induced transcriptional changes in the ovary as they relate to previously described impacts on serum estradiol concentrations and altered follicular development in zebrafish. In-silico computational approaches were ...

  4. TCDD and corticosterone on testicular steroidogenesis and antioxidant system of epididymal sperm in rats.

    Science.gov (United States)

    Dhanabalan, S; Mathur, P P; Latha, P

    2015-09-01

    2,3,7,8-Tetrachloro dibenzo-p-dioxin (TCDD), an endocrine-disrupting environmental pollutant, has been found to cause male reproductive toxicity. Glucocorticoids have been found to influence the metabolic pathway of TCDD. Stress, which affects the male reproductive function, is marked by an increase in the level and activity of glucocorticoids in the body. The present study was carried out to understand the effect of TCDD on testicular steroidogenesis and sperm antioxidant system under the influence of increased level of corticosterone in the body. Adult male rats were treated with either TCDD (100 ng/kg bw/ day) or corticosterone (3 mg/kg bw/day) or both for 15 days. Treatment with either TCDD or corticosterone was found to suppress the levels of steroidogenic acute regulatory protein and androgen-binding protein and reduce the activities of steroidogenic enzymes in testis while increasing oxidative stress in ventral prostate, seminal vesicles and epididymal sperm. In rats treated with both TCDD and corticosterone, the suppression of testicular steroidogenesis and increase in oxidative stress observed in ventral prostate, seminal vesicles and epididymal sperm were significant as compared to TCDD alone treated rats. The levels of Fas and FasL proteins were also increased in rats subjected to either TCDD or corticosterone treatment. In rats treated with both compounds, the increase observed in testicular levels of Fas and FasL was significant as compared to TCDD alone treated rats. Effect of TCDD on testicular steroidogenesis and antioxidant system of epididymal sperm may get enhanced under increased level of glucocorticoids in the body.

  5. Consequences of TCDD treatment on intra-hepatic lymphocytes during liver regeneration.

    Science.gov (United States)

    Horras, Christopher J; Lamb, Cheri L; King, Allie L; Hanley, Jason R; Mitchell, Kristen A

    2012-01-01

    Increasing evidence demonstrates a physiological role for the aryl hydrocarbon receptor (AhR) in regulating hepatocyte cell cycle progression. Previous studies have used a murine model of liver regeneration to show that exposure to the potent exogenous AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), suppresses hepatocyte proliferation in vivo. Based on recent reports that natural killer (NK) cells negatively regulate liver regeneration, coupled with the well-established immunomodulatory effects of TCDD, it was hypothesized that alterations in lymphocyte activation contribute to the suppression of liver regeneration in TCDD-treated mice. To test this, mice were treated with TCDD (20 μg/kg) 1 day prior to 70% partial hepatectomy (PH), in which two-thirds of the liver was surgically resected. Lymphocytes were collected from the remnant liver and analyzed by flow cytometry. Whereas exposure to TCDD did not alter the number of NK cells or CD3(+) T-cells recovered from the regenerating liver, it reduced the percentage and number of intra-hepatic NKT cells 42 h after PH. With regard to lymphocyte activation, TCDD treatment transiently increased CD69 expression on NK and NKT cells 12 h after PH, but had no effect on intracellular levels of IFNγ in NK, NKT, or CD3(+) T-cells. To determine the relevance of NK cells to the suppression of liver regeneration by TCDD, mice were treated with anti-Asialo GM-1 (ASGM-1) antibody to deplete NK cells prior to TCDD treatment and PH, and hepatocyte proliferation was measured using bromodeoxyuridine incorporation. Exposure to TCDD was found to inhibit hepatocyte proliferation in the regenerating liver of NK cell-depleted mice and control mice to the same extent. Hence, it is unlikely that enhanced numbers or increased activation of NK cells contribute to the suppression of liver regeneration in TCDD-treated mice.

  6. In vitro Cytotoxicity of TCDD on SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective The toxicology of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has been studied mainly with regard to the carcinogenicity of its metabolites, but its phototoxicity is not well understood. Although some studies have indicated the lethal phototoxicity of TCDD, this study was designed to investigate its effect on SPC-A1 cells. Methods SPC-A1 cells were cultured in 1640 medium and treated with 10 nmol/L, 0.1 μmol/L, 1 μmol/L TCDD for either 24 h or 96 h at each concentration. SPC-A1 cells were co-cultured with TCDD at different concentrations. Then the cell morphology, DNA fragment electrophoresis, and cell cycle were analyzed by flow cytometry, and enzyme assays were used to observe the effect of TCDDon the morphology, growth rate, and enxyme change of SPC-A1 cells. Results With the increasing concentrations of TCDD and prolongation of culture time, the morphology of SPC-A1 cells was changed from round shape to spindle, and the ability of SPC-A1 cells to adhere to wall was decreased. With debris emitted around the cells, the morphologic changes included reduction in cell volume. Nuclear chromatin condensation and PI were observed. With the increasing concentrations of TCDD,DNA ladder occurred. After treatment with TCDD, extraction of cancer cells exhibited typical DNA fragmentation, and flow cytometry analysis showed apoptosis in a dose-dependent manner. As the concentration of TCDD rose from 10 nmol/L to 1 μmol/L, the ratio of apoptotic cells increased from 10.76% to 21.82%. Conclusions TCDD has in vitro cytotoxicity on SPC-A1 cells, and the cytotoxicity is positively related to its concentration and culture time. TCDD may inhibit the growth and proliferation of SPC-A 1 cells through the pathway of apoptosis introduction.

  7. [Effects of early postnatal exposure to dieldrin on synaptic development of striatum in mice].

    Science.gov (United States)

    Gao, Ye; Wang, Qu-nan; Wu, Shan

    2012-02-01

    To investigate the effects of early postnatal exposure to dieldrin on striatum synaptic development in lactation, adolescence and adulthood of mice. The pups were divided into 5 groups randomly. Three groups were exposed to dieldrin (0.01% DMSO solution) at doses of 0.2, 2.0 and 20.0 microg/kg and two control groups were exposed to DMSO or saline by intraperitoneal injection of every other day from postnatal days (PND) 3 to PND13. The striatum were isolated from brain in lactation (PND14), adolescence (PND36) and adulthood (PND98). Western blot assay was used to detect the expression levels of striatal synaptic proteins. The postnatal exposure to dieldrin could reduce the level of growth associated protein (GAP43) of striatum in lactation in a dose-dependent manner. In adolescence, the level of glial fibrillary acidic protein (GFAP) in striatum increased and the levels of tyrosine hydroxylase (TH), GAP43 and post-synaptic density protein 95 (PSD95) decreased with exposure doses. The level of Synapsin I decreased in adolescence male mice. The changes of expression levels of GFAP, TH and PSD95 proteins lasted to adulthood. Early postnatal exposure to dieldrin could affect the expression level of GAP43 protein in striatum. The expression levels of TH and PSD95 proteins in striatum decreased in adolescence and adulthood. These results indicated that the early postnatal exposure to dieldrin may persistently interfere in the striatal synaptic development.

  8. Removal of dieldrin from aqueous solution by a novel triolein-embedded composite adsorbent.

    Science.gov (United States)

    Ru, Jia; Liu, Huijuan; Qu, Jiuhui; Wang, Aimin; Dai, Ruihua

    2007-03-06

    In this study, a novel triolein-embedded activated carbon composite adsorbent (CA-T) was prepared and applied for the adsorption and removal of dieldrin from aqueous systems. Experiments were carried out to investigate the adsorption behavior of dieldrin on CA-T, including adsorption isotherms, adsorption kinetics, the influence of initial concentration, temperature, shaking speed, pH and the addition of humic acid (HA) on adsorption. The adsorption isotherms accorded with Freundlich equation. Three kinetics models, including pseudo-first-order, pseudo-second-order and intraparticle diffusion models, were used to fit the experimental data. By comparing the correlation coefficients, it was found that both pseudo-second-order and intraparticle diffusion models were used to well describe the adsorption of dieldrin on CA-T. The addition of HA had little effect on dieldrin adsorption by CA-T. Results indicated that CA-T appeared to be a promising adsorbent for removing lipophilic dieldrin in trace amount, which was advantageous over pure granular activated carbon (GAC). The adsorption rate increased with increasing shaking speed, initial concentration and temperature, and remained almost unchanged in the pH range of 4-8. Thermodynamic calculations indicated that the adsorption reaction was spontaneous with a high affinity and the adsorption was an endothermic reaction.

  9. Preliminary note on potential use of forage crops for soil phytoremediation of dieldrin.

    Science.gov (United States)

    Donnarumma, L; Annesi, T; Pompi, V; Rosati, S; Conte, E

    2010-01-01

    The aim of this trial was to evaluate the feasibility of using tall fescue (Festuca arundinacea) and alfalfa (Medicago sativa) for phytoremediation of dieldrin. Experimental trial was carried out in greenhouse with temperature and light control. Each tested crop were seeded in individual pots (10 plants/pot) filled with contaminated soil (47 microg/kg dieldrin) and uncontaminated soil collected in sites located in the province of Latina (Italy). Samples of soil, root, and aerial part of plants were analysed at 3 and 6 months after seeding. The analytical determinations in soil and plant samples were carried out by GLC-ECD and confirmed by GLC-MS. After 6 months in the greenhouse, recoveries of dieldrin from soil planted with tall fescue and alfalfa were significantly lower than recoveries in unplanted control soil. Dieldrin residue values in root did not differ between the two different sampling times for each forage crop tested, but they were always higher in fescue than in alfalfa. Residue levels in aerial part were low (dieldrin in soil at low level of contamination.

  10. Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations.

    Science.gov (United States)

    Fowler, Paul A; Abramovich, David R; Haites, Neva E; Cash, Phillip; Groome, Nigel P; Al-Qahtani, Ahmed; Murray, Tessa J; Lea, Richard G

    2007-11-01

    Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis. Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated. Exposure to dieldrin reduced LH-induced testosterone secretion (P Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals. Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.

  11. Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system.

    Science.gov (United States)

    Hatcher, Jaime M; Richardson, Jason R; Guillot, Thomas S; McCormack, Alison L; Di Monte, Donato A; Jones, Dean P; Pennell, Kurt D; Miller, Gary W

    2007-04-01

    Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. Alpha-synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by (3)H-WIN 35,428 binding and (3)H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD.

  12. Aldrin and dieldrin: a reevaluation of the cancer and noncancer dose-response assessments.

    Science.gov (United States)

    Hooker, Eric P; Fulcher, Keri G; Gibb, Herman J

    2014-05-01

    The dose-response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg-day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg-day)(-1), respectively (i.e., about 5- and 2.3-fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA. © 2013 Society for Risk Analysis.

  13. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver phosphoenolpyruvate carboxykinase (PEPCK) activity, glucose homeostasis and plasma amino acid concentrations in the most TCDD-susceptible and the most TCDD-resistant rat strains

    Energy Technology Data Exchange (ETDEWEB)

    Viluksela, M.; Pohjanvirta, R.; Tuomisto, J.T.; Tuomisto, J. (National Public Health Inst., Laboratory of Toxicology, Kuopio (Finland)); Unkila, M. (Department of Pharmacology and Toxicology, Univ. of Kuopio (Finland)); Stahl, B.U.; Rozman, K.K. (Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States) Section of Environmental Toxicology, GSF-Institut fuer Toxikologie, Neuherberg (Germany))

    1999-08-01

    Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of reduced gluconeogenesis by comparing dose-responses and time-courses of effects of TCDD on the activity of phosphoenolpyruvate carboxykinase (PEPCK) in liver, liver glycogen concentration as well as plasma concentrations of glucose and amino acids in both genders of TCDD-sensitive Long-Evans (L-E) rats and TCDD-resistant Han/Wistar (H/W) rats. A dose-dependent decrease in PEPCK activity was observed in H/W rats, but in L-E rats the activity was not decreased. However, TCDD impaired the strong increase in liver PEPCK activity observed in pair-fed controls of the L-E strain. Liver glycogen concentrations were severely decreased in L-E rats and moderately in H/W rats. This effect seems to be secondary to reduced feed intake, since a similar decrease was seen in pair-fed controls. Decreases in plasma glucose concentrations were also more profound in L-E rats than in H/W rats, but pair-fed controls were generally less affected. Circulating concentrations of amino acids were markedly increased in TCDD-treated L-E rats, which is likely to reflect increased mobilization of amino acids and their decreased metabolism in liver. Reduction of liver PEPCK activity cannot account for the sensitivity difference of these two strains of rats in terms of mortality. Nevertheless, the response of both strains of TCDD-treated rats regarding gluconeogenesis is different from that seen in pair-fed controls and suggesting that impairment of this pathway contributes to the development of the wasting syndrome. (orig.) With 7 figs., 2 tabs., 47 refs.

  14. Interactions of Penicillium griseofulvum with inorganic and organic substrates: vanadium, lead and hexachlorocyclohexane

    Science.gov (United States)

    Ceci, Andrea; Pierro, Lucia; Riccardi, Carmela; Maggi, Oriana; Pinzari, Flavia; Gadd, Geoffrey Michael; Petrangeli Papini, Marco; Persiani, Anna Maria

    2015-04-01

    Soil is an essential and non-renewable resource for human beings and ecosystems. In recent years, anthropogenic activities mainly related to hydrocarbon fuel combustion, mining and industrial activities have increased the levels of vanadium in the environment, raising concern over its spread. Vanadium may be essential for some bacteria and fungi, but can have toxic effects at high concentrations. The pesticide lindane or γ-hexachlorocyclohexane (γ-HCH) and another two isomers of hexachlorocyclohexane (HCH), α-HCH, and β-HCH, were included as persistent organic pollutants in the Stockholm Convention in 2008, and their worldwide spread and toxic effects on organisms are severe environmental problems. Fungi play important roles in soil and can survive in high concentrations of toxic elements and pesticides by possessing mechanisms for the degradation, utilization and transformation of organic and inorganic substrates. The transformation of potentially toxic elements (PTEs), and degradation of chlorinated pesticides and other persistent organic pollutants may provide environmentally-friendly and economical approaches for environmental management and restoration. In this work, we have investigated the tolerance of a soil fungal species, Penicillum griseofulvum, to different hexachlorocyclohexane (HCH) isomers, α-HCH, β-HCH, δ-HCH and γ-HCH or lindane, and two PTEs, vanadium and lead in relation to growth responses and biotransformation. P. griseofulvum was isolated from soils with high levels of PTEs (including vanadium and lead), and HCH residues. P. griseofulvum was able to tolerate vanadium concentrations up to 5 mM, combinations of 2.5 mM vanadium and lead compounds, and was able to grow in the presence of a 4 mg L-1 mixture of α-HCH, β-HCH, δ-HCH and γ-HCH, and degrade these substrates. Tolerance mechanisms may explain the occurrence of fungi in polluted habitats: their roles in the biotransformation of metals and persistent organic pollutants may

  15. Assessment of the levels of hexachlorocyclohexane in blood samples from Mexico.

    Science.gov (United States)

    Trejo-Acevedo, Antonio; Rivero-Pérez, Norma Edith; Flores-Ramirez, Rogelio; Orta-García, Sandra Teresa; Pruneda-Álvarez, Lucia Guadalupe; Pérez-Maldonado, Iván N

    2012-06-01

    The aim of this study was to evaluate hexachlorocyclohexane (HCH) exposure in children living in nine hot spots in four Mexican states. We analyzed HCH (α, β, and γ-isomers) in blood using gas chromatography/mass spectrometry. HCH exposure level in 261 children was assessed and approximately 75 % of the children studied had detectable levels of HCH. These levels ranged from 188 to 40,096.7 ng/g lipid. The highest mean levels were found in Lacanja (5,446.9 ng/g lipid), an indigenous community in Chiapas, Mexico. Our data indicate high exposure to HCH in children living in these communities.

  16. Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus.

    Science.gov (United States)

    Martyniuk, Christopher J; Feswick, April; Spade, Daniel J; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2010-08-01

    Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis, but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after 7 days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20-30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (pdieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer's disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are also associated with the etiology of human neurological disorders. (c) 2010 Elsevier Inc. All rights reserved.

  17. Anopheles arabiensis sperm production after genetic manipulation, dieldrin treatment, and irradiation.

    Science.gov (United States)

    Damiens, D; Vreysen, M J B; Gilles, J R L

    2013-03-01

    The use of the sterile insect technique relies on the release of sterilized mass-reared male insects which, before field releases, endure several unnatural treatments. In the case of Anopheles arabiensis (Patton) sterile insect technique program in Sudan, the genetic background of the original strain was first changed to create a genetic sexing strain that is based on a dieldrin-resistant mutation. Secondly, the eggs of the genetic sexing strain require treatment with dieldrin to allow complete elimination of female L1 larvae to enable the release of males only. Finally, male mosquitoes receive an irradiation dose of 70 Gy as pupae for sterilization. The effects of these treatments on sperm production were tested separately and in combination. Irradiation alone significantly decreased the initial sperm number and prevented new sperm production. However, the dieldrin treatment, aimed at eliminating females, appears to have an unexpected radioprotectant effect.

  18. Chlorobenzenes, lindane and dieldrin induce apoptotic alterations in human peripheral blood lymphocytes (in vitro study).

    Science.gov (United States)

    Michałowicz, Jaromir; Mokra, Katarzyna; Rosiak, Karolina; Sicińska, Paulina; Bukowska, Bożena

    2013-11-01

    In this study, we have assessed apoptotic effect of 1,2,4-trichlorobenzene, hexachlorobenzene, lindane and dieldrin on human peripheral blood lymphocytes. We observed an increase in ROS formation and a decrease in mitochondrial transmembrane potential in the cells incubated with low concentrations of all compounds studied, in particular lindane and dieldrin. ROS formation and changes in mitochondrial transmembrane potential may have influenced caspase-3 activation, a crucial enzyme in the apoptotic process. Moreover, chlorobenzenes, and in particular lindane and dieldrin changed cells' membrane permeability and induced phosphatidylserine translocation, which confirmed that they are capable of inducing apoptosis in human lymphocytes. Apoptotic changes in human lymphocytes provoked by biologically relevant concentrations of these substances suggest that they may disturb function of immunological system especially among people occupationally exposed to their action. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Beneficial effects of carnosic acid on dieldrin-induced dopaminergic neuronal cell death.

    Science.gov (United States)

    Park, Jeong Ae; Kim, Seung; Lee, Sook-Young; Kim, Chun-Sung; Kim, Do Kyung; Kim, Sung-Jun; Chun, Hong Sung

    2008-08-27

    Carnosic acid (CA) is one of the bioactive polyphenols present in extracts of the herb rosemary (Rosmarinus officinalis). In this study, we examined possible protective effects of CA on neurotoxicity induced by dieldrin, an organochlorine pesticide implicated in sporadic Parkinson's disease, in cultured dopaminergic cells (SN4741). CA (5-10 muM) pretreatment showed potent protective effects in a concentration-related manner and prevented dieldrin (10 muM)-induced caspase-3 activation, Jun N-terminal kinase phosphorylation, and caspase-12 activation. Furthermore, dieldrin-induced downregulation of brain-derived neurotrophic factor production was significantly attenuated by CA. These results suggest that CA may safeguard dopaminergic neuronal cells from environmental neurotoxins by enhancing brain-derived neurotrophic factor and repressing apoptotic molecules.

  20. TCDD promotes lung tumors via attenuation of apoptosis through activation of the Akt and ERK1/2 signaling pathways.

    Directory of Open Access Journals (Sweden)

    Rong-Jane Chen

    Full Text Available 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one of the tumor-promoting mechanisms regulated by TCDD. We performed an additional series of experiments in the normal human bronchial epithelial cell line Beas2B cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our in vitro results confirmed that TCDD could rescue cells from apoptosis induced by staurosporine. The inhibition of apoptosis is likely mediated by the activation of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway-specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part, through the Akt and ERK1/2 signaling pathways.

  1. TCDD promotes lung tumors via attenuation of apoptosis through activation of the Akt and ERK1/2 signaling pathways.

    Science.gov (United States)

    Chen, Rong-Jane; Siao, Shih-He; Hsu, Chung-Huei; Chang, Chu-Yung; Chang, Louis W; Wu, Chih-Hsiung; Lin, Pinpin; Wang, Ying-Jan

    2014-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one of the tumor-promoting mechanisms regulated by TCDD. We performed an additional series of experiments in the normal human bronchial epithelial cell line Beas2B cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our in vitro results confirmed that TCDD could rescue cells from apoptosis induced by staurosporine. The inhibition of apoptosis is likely mediated by the activation of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway-specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part, through the Akt and ERK1/2 signaling pathways.

  2. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qing [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States); Rise, Matthew L. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Spitsbergen, Jan M. [Department of Microbiology, Oregon State University, 220 Nash Hall, Corvallis, OR 97331 (United States); Hori, Tiago S. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Mieritz, Mark; Geis, Steven [Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706 (United States); McGraw, Joseph E. [School of Pharmacy, Concordia University Wisconsin, 12800 North Lake Shore Drive, Mequon, WI 53097 (United States); Goetz, Giles [School of Aquatic and Fishery Sciences, University of Washington, 1122 Northeast Boat Street, Seattle, WA 98195 (United States); Larson, Jeremy; Hutz, Reinhold J. [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); Carvan, Michael J., E-mail: carvanmj@uwm.edu [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States)

    2013-09-15

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  3. Reevaluation of the developmental toxicity of dieldrin by the use of fertilized Japanese quail eggs.

    Science.gov (United States)

    Kamata, Ryo; Shiraishi, Fujio; Takahashi, Shinji; Shimizu, Akira; Shiraishi, Hiroaki

    2010-06-01

    To reevaluate the toxicity of the organochlorine insecticide and persistent organic pollutant dieldrin and confirm its impact on development, an exposure trial using bird eggs was performed. Dieldrin at concentrations of 10-100 microg/g of egg was injected into the yolks of Japanese quail (Coturnix japonica) eggs. Hatchlings from the eggs were raised to sexual maturity and multiple tests to detect the harmful effects of dieldrin were conducted. Dieldrin at 100 microg/g decreased egg hatchability by 50.0% (vehicle control, 86.7%), although embryogenesis even in unhatched eggs treated with high doses of dieldrin was normal. In safely hatched chicks, dose-dependent early death with tonic seizure was observed and all birds exposed to 100 microg/g died within 3 days. Other significant alterations in hatchlings were enlargement of the whole brain, decreases in mRNA expressions of tryptophan hydroxylase in the brainstem and cholesterol side-chain cleavage in the male gonad, and increases in mRNA expressions of cytochrome P450 1A and 2C18 in the liver. For mature birds (males at 5 weeks and females at 10 weeks of age), impairment of eggshell formation such as reduced eggshell mass and eggshell thinning, increases in the body mass of males and the liver mass of females and increases in serum total cholesterol and triglyceride concentrations were observed. The results indicated that not only does the neurotoxicity of dieldrin bring early death, but its effects on reproductive and hepatic functions (detected as gene transcriptional changes in hatchlings) persist harmfully after maturity. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Acute effects of TCDD administration:special emphasis on testicular and sperm mitochondrial function

    Institute of Scientific and Technical Information of China (English)

    Paula C Mota; Renata S Tavares; Marlia Cordeiro; Susana P Pereira; Stephen J Publicover; Paulo J Oliveira; Joo Ramalho-Santos

    2012-01-01

    Objective: The goal of this study was to verify if 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could have any effect on male germ cells mitochondria and in this way add new insights in how male reproductive alterations observed in other studies occur. Methods:In vivo and in vitro approaches using rat testis and human sperm as models were employed to evaluate TCDD effects on testicular and sperm mitochondria after 24 h of exposure. Results:Testicular mitochondria from TCDD-treated rats presented no differences in the bioenergetic parameters monitored except for a significantly higher electric membrane potential in the presence of ADP, corroborated when TCDD was directly added to testicular mitochondria from untreated rats. Nevertheless, sperm mitochondrial membrane potential, motility, viability, capacitation and acrosomal integrity did not change after TCDD treatment. Moreover, only few sperm cells exposed to TCDD increased their intracellular Ca2+concentration. Conlusions:TCDD can interact directly with rat testicular mitochondria inducing small changes. This effect, however, does not seem to occur in human sperm or it may be insufficient to induce significant alterations as observed by the maintenance of sperm function.

  5. The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) in TCDD-induced porphyria

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Cheng Catsby.

    1989-01-01

    Halogenated aryl hydrocarbon(HAH)-induced porphyria is caused by alteration of porphyrin metabolism and results in the accumulation of hepatic and urinary porphyrins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (75 {mu}/kg) caused significant increases of hepatic porphyrin levels in C57BL/6 male, female and ovariectomized female, and C57BL/10 male mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 {mu}mol/kg. Cotreatment with MCDF (750 {mu}mol/kg) and 2,3,7,8-TCDD (75 {mu}g/kg) resulted in partial antagonism of 2,3,7,8-TCDD-induced porphyrin accumulation in female but not in male mice. In female C57BL/6 mice, 2,3,7,8-TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the inhibition of uroporphyrinogen decarboxylase (UROD) activity. MCDF (750 {mu}mol/kg) did not significantly affect these enzyme activities. In coadministration studies, MCDF partially antagonized 2,3,7,8-TCDD-induced hepatic porphyrin accumulation but did not affect the activities of hepatic AHH, EROD or UROD. These results demonstrate that the induction of the monooxygenase enzyme activities and the inhibition of UROD activity by 2,3,7,8-TCDD and the development of porphyria are not coordinately regulated in C57BL/6 female mice. In cultured chick embryo hepatocytes, 2,3,7,8-TCDD caused a significant increase in porphyrin levels and induced AHH and EROD activities. MCDF and Aroclor 1254 partially antagonized the 2,3,7,8-TCDD induced AHH and EROD activities but not the porphyrin accumulation.

  6. Cross-resistance with dieldrin of a novel tricyclic dinitrile GABA receptor antagonist

    Science.gov (United States)

    Matsuda, Kazuhiko; Hosie, Alastair M; Holyoke, Caleb W; Rauh, James J; Sattelle, David B

    1999-01-01

    A novel tricyclic dinitrile, KN244, blocked the wild-type (dieldrin-sensitive) homo-oligomeric γ-aminobutyric acid (GABA)-gated chloride channel of Drosophila melanogaster expressed in Xenopus oocytes. Sensitivity to the block by KN244 of the response to 30 μM GABA (IC50=41.6 nM, wild-type RDLac) was reduced abut 100 fold (IC50=4.5 μM) in the dieldrin-resistant (RDLacA302S) form of RDL. PMID:10455279

  7. A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer.

    Science.gov (United States)

    Chang, Ellen T; Boffetta, Paolo; Adami, Hans-Olov; Cole, Philip; Mandel, Jack S

    2014-10-01

    To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case-control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case-control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.

  8. Aryl Hydrocarbon Receptors in the frog Xenopus laevis: Two AHR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    OpenAIRE

    Lavine, Jeremy A.; Rowatt, Ashley J.; Klimova, Tatyana; Whitington, Aric J.; Dengler, Emelyne; Beck, Catherine; Powell, Wade H.

    2005-01-01

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates. However, frogs are relatively insensitive to TCDD toxicity, especially during early life stages. Toxicity of TCDD and related halogenated aromatic hydrocarbons is mediated by the aryl hydrocarbon receptor (AHR), and specific differences in properties of the AHR signaling pathway can underlie differences in TCDD toxicity in different species. This study investigated the role of AHR in frog TCDD i...

  9. Pretreatment with TCDD exacerbates liver injury from Concanavalin A: critical role for NK cells.

    Science.gov (United States)

    Fullerton, Aaron M; Roth, Robert A; Ganey, Patricia E

    2013-11-01

    For many liver diseases, including viral and autoimmune hepatitis, immune cells play an important role in the development and progression of liver injury. Concanavalin A (Con A) administration to rodents has been used as a model of immune-mediated liver injury resembling human autoimmune hepatitis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to alter the development of immune-mediated diseases. Mice pretreated with TCDD developed exacerbated liver injury in response to administration of a mild dose (6 mg/kg) of Con A. In the present study, we tested the hypothesis that TCDD pretreatment exacerbates Con A-induced liver injury by enhancing the activation and recruitment of accessory cell types including neutrophils, macrophages, and natural killer (NK) cells. Mice were treated with 0, 0.3, 3, or 30 μg/kg TCDD and 4 days later with Con A or saline. TCDD pretreatment with doses of 3 and 30 μg/kg significantly increased liver injury from Con A administration. The plasma concentrations of neutrophil chemokines were significantly increased in TCDD-pretreated mice after Con A administration. NKT cell-deficient (CD1d KO) mice were used to examine whether NKT cells were required for TCDD/Con A-induced liver injury. CD1d KO mice were completely protected from liver injury induced by treatment with Con A alone, whereas the injury from TCDD/Con A treatment was reduced but not eliminated. However, T-cell deficient (RAG1 KO) mice were protected from liver injury induced by Con A irrespective of pretreatment with TCDD. TCDD/Con A treatment increased the percentage of NK cells expressing the activation marker CD69. Depletion of NK cells prior to treatment resulted in significant reductions in plasma interferon-γ and liver injury from TCDD/Con A treatment. In summary, exposure to TCDD exacerbated the immune-mediated liver injury induced by Con A, and our findings suggest that NK cells play a critical role in this response.

  10. Conceptual Optimisation of the TDI and TCDD Protections for LHC Injection Lines

    CERN Document Server

    Sala, P R; CERN. Geneva. AB Department

    2003-01-01

    The TDI (Injection Stoppers) and TCDD (Injection Collimators) for LHC are mobile beam obstacles that will protect the superconducting machine elements during injection. Simulations have been performed to investigate the TDI and TCDD performances and optimise their design. Mechanical aspects are not treated in the present work, and further definition of the details of the design is left to a conclusive report. The need for the TCDD collimator has been demonstrated. The original design goal, that was to prevent quenches in pilot bunch operation and damage in all faulty conditions, has been upgraded to prevent quenches in all cases not involving a MKI (Injection kicker) failure.

  11. Strong Associations Between the Pesticide Hexachlorocyclohexane and Type 2 Diabetes in Saudi Adults

    Directory of Open Access Journals (Sweden)

    Abdulaziz Al-Othman

    2014-08-01

    Full Text Available Pesticide exposure has been implicated as an environmental risk factor for the development of type 2 diabetes mellitus (T2DM. The aim of this study was to investigate the association of the body burden of the pesticide hexachlorocyclohexane (HCH with the risk of T2DM in a sample of adults from Saudi Arabia. Serum samples were obtained from 280 adult subjects. Hexachlorocyclohexane isomer residues were measured by high-resolution gas chromatography-mass spectrometry. Data on lifestyle, dietary habits, and health status were gathered. Associations between exposure and T2DM were analyzed by logistic regression. Around 49% of adults enrolled in this study were diagnosed with T2DM. Among various HCH isomers, serum concentrations of the pesticides β and γ-HCH were most strongly and consistently linked to T2DM in our studied subjects. Associations of HCH varied across five components of the metabolic syndrome. It positively and significantly associated with four out of the five components, especially elevated triglycerides, high fasting glucose, high blood pressure and HOMA-IR but negatively and significantly with HDL-cholesterol. This study in line with earlier ones about diabetes associated with HCH pesticide exposure and proposes possible hormonal pathways worthy of further investigation.

  12. Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

    Science.gov (United States)

    Lamb, Cheri L.; Cholico, Giovan N.; Perkins, Daniel E.; Fewkes, Michael T.; Oxford, Julia Thom; Lujan, Trevor J.; Morrill, Erica E.

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury. PMID:27672655

  13. Plasma cytokine concentrations in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD

    Directory of Open Access Journals (Sweden)

    Fatemeh eSaberi Hosnijeh

    2012-04-01

    Full Text Available ObjectivesFew epidemiological studies have studied the effect of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD on blood cytokine levels. In this study we investigated changes in plasma levels of a large panel of cytokines, chemokines and growth factors among workers from a Dutch historical cohort occupationally exposed to chlorophenoxy herbicides and contaminants including TCDD.MethodsEighty-five workers who had been exposed to either high (n=47 or low (n=38 TCDD levels more than 30 years before serum collection were included in the current investigation. Plasma level of 16 cytokines, 10 chemokines and 6 growth factors were measured. Current plasma levels of TCDD (TCDDCurrent were determined by high resolution gas chromatography/isotope dilution high resolution mass spectrometry. TCDD blood levels at the time of last exposure (TCDDmax were estimated using a one-compartment first order kinetic model. ResultsBlood levels of most analytes had a negative association with current and estimated past maximum TCDD levels. These decreases reached formal statistical significance for fractalkine, transforming growth factor alpha (TGF-α and fibroblast growth factor 2 (FGF2 with increasing TCDD levels.ConclusionsOur study showed a general reduction in most analyte levels with the strongest effects for fractalkine, FGF2 and TGF-α. These findings suggest that TCDD exposure could suppress the immune system and that chemokine and growth factor-dependent cellular pathway changes by TCDD may play role in TCDD toxicity and associated health effects.

  14. TCDD dysregulation of 13 AHR-target genes in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Watson, John D., E-mail: john.watson@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Prokopec, Stephenie D., E-mail: stephenie.prokopec@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Smith, Ashley B., E-mail: ashleyblaines@gmail.com [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Okey, Allan B., E-mail: allan.okey@utoronto.ca [Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio (Finland); Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki (Finland); Boutros, Paul C., E-mail: paul.boutros@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2014-02-01

    Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long–Evans (Turku/AB; L–E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000 μg/kg at 19 h after TCDD exposure and time points ranging from 1.5 to 384 h after exposure to 100 μg/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose–response analysis, none had an ED{sub 50} equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10–100 fold higher, in at least one strain (Ahrr (L–E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L–E), Inmt (both), Nfe2l2 (L–E), Nqo1 (L–E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities. - Highlights: • NanoString measured hepatic mRNA molecules

  15. REPRODUCTIVE TOXICITY OF CHLORPYRIFOS, DIELDRIN, AND METHYL MERCURY MIXTURES TO THE AMPHIPOD, HYALELLA AZTECA

    Science.gov (United States)

    Toxicological interactions were assessed on the reproduction of the amphipod Hyalella azteca throughout a chronic exposure to methyl mercury (0.9, 4.7, 23.3 nM), chlorpyrifos (0.01, 0.05, 0.24), dieldrin (0.5, 2.3, 11.4 nM) and their binary mixtures. H. azteca were exposed to the...

  16. Mortality of workers exposed to dieldrin and aldrin: a retrospective cohort study.

    Science.gov (United States)

    de Jong, G; Swaen, G M; Slangen, J J

    1997-01-01

    OBJECTIVE: To investigate the occurrence of long term health effects in humans exposed to aldrin and dieldrin, with an update of an earlier retrospective cohort mortality study. METHODS: A group of 570 workers employed between 1 January 1954 and 1 January 1970 either in a production or formulation plant were followed up for mortality until 1 January 1993. There were extensive industrial hygiene data available and biological monitoring data of aldrin and dieldrin for most of the workers. From these data individual estimates were made of the total intake of dieldrin. A total number of 2539.37 person-years at risk was added to the original study. RESULTS: 118 deaths were observed compared with 156 expected. No increase in mortality from liver cancer was found. However, there was an excess in mortality from rectal cancer. This excess was inversely related to the dose gradient. An analysis by job title did not show any excess cancer in any particular job. CONCLUSION: The study does not support a carcinogenic effect of dieldrin and aldrin in humans. PMID:9404316

  17. TCDD dysregulation of 13 AHR-target genes in rat liver.

    Science.gov (United States)

    Watson, John D; Prokopec, Stephenie D; Smith, Ashley B; Okey, Allan B; Pohjanvirta, Raimo; Boutros, Paul C

    2014-02-01

    Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long-Evans (Turku/AB; L-E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000μg/kg at 19h after TCDD exposure and time points ranging from 1.5 to 384h after exposure to 100μg/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose-response analysis, none had an ED50 equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10-100 fold higher, in at least one strain (Ahrr (L-E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L-E), Inmt (both), Nfe2l2 (L-E), Nqo1 (L-E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities.

  18. Prenatal low dosage dioxin (TCDD) exposure impairs cochlear function resulting in auditory neuropathy.

    Science.gov (United States)

    Safe, Theresa M; Luebke, Anne E

    2016-01-01

    2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD), a ubiquitous and persistent environmental contaminant, is a potent teratogen. Whereas developmental TCDD toxicity is mediated by the aryl hydrocarbon receptor (AhR), the normal function of the AhR is poorly understood. We tested whether dioxin exposure during a critical period of hair cell development disrupts cochlear function in three mouse strains, (C57BL6, BalbC, and CBA) that contain high affinity AhR-b alleles. C57BL/6, BalbC, and CBA dams were exposed to 500 ng/kg TCDD or olive oil (vehicle) on embryonic day 12 by gavage. Cochlear function was analyzed at 1.5 months of age by measuring 1) auditory brainstem response (ABRs) to tone pips from 5.6 to 30 kHz, and 2) distortion-product otoacoustic emissions (DPOAEs) evoked by primaries with f2 at the same frequency values. Cochlear threshold sensitivity following TCDD exposure was significantly elevated in both female and male mice in the C57BL/6 strain, carrying the Ahb-1 allele, but not significantly elevated in the BalbC or CBA strains, carrying the Ahb-2 allele. These ABR threshold deficits in mice carrying the Ahb-1 allele parallels the cleft palate incidence to higher TCDD exposures, suggesting that ABR testing could serve as a sensitive indicator of TCDD toxicity in at-risk children. Moreover, DPOAEs were not affected following TCDD exposure in any of the mouse strains, suggesting that following TCDD exposure mice with the Ahb-1 allele exhibit a mild auditory neuropathy. The causes of many auditory neuropathies are unknown, yet a developmental exposure to dioxin may be a risk factor for this condition.

  19. Prenatal Low Dosage Dioxin (TCDD) Exposure Impairs Cochlear Function Resulting in Auditory Neuropathy

    Science.gov (United States)

    Safe, Theresa M.; Luebke, Anne E.

    2015-01-01

    2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD), a ubiquitous and persistent environmental contaminant, is a potent teratogen. Whereas developmental TCDD toxicity is mediated by the aryl hydrocarbon receptor (AhR), the normal function of the AhR is poorly understood. We tested whether dioxin exposure during a critical period of hair cell development disrupts cochlear function in three mouse strains, (C57BL6, BalbC, and CBA) that contain high affinity AhR-b alleles. C57BL/6, BalbC, and CBA dams were exposed to 500 ng/kg TCDD or olive oil (vehicle) on embryonic day 12 by gavage. Cochlear function was analyzed at 1.5 months of age by measuring 1) auditory brainstem response (ABRs) to tone pips from 5.6 to 30 kHz, and 2) distortion-product otoacoustic emissions (DPOAEs) evoked by primaries with f2 at the same frequency values. Cochlear threshold sensitivity following TCDD exposure was significantly elevated in both female and male mice in the C57BL/6 strain, carrying the Ahb-1 allele, but not significantly elevated in the BalbC or CBA strains, carrying the Ahb-2 allele. These ABR threshold deficits in mice carrying the Ahb-1 allele parallels the cleft palate incidence to higher TCDD exposures, suggesting that ABR testing could serve as a sensitive indicator of TCDD toxicity in at-risk children. Moreover, DPOAEs were not affected following TCDD exposure in any of the mouse strains, suggesting that following TCDD exposure mice with the Ahb-1 allele exhibit a mild auditory neuropathy. The causes of many auditory neuropathies are unknown, yet a developmental exposure to dioxin may be a risk factor for this condition. PMID:26464051

  20. Developmental Exposure to TCDD Reduces Fertility and Negatively Affects Pregnancy Outcomes across Multiple Generations

    OpenAIRE

    Bruner-Tran, Kaylon L.; Osteen, Kevin G.

    2010-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Since humans and animals are most sensitive to toxicant exposure during development, we previously developed a mouse model of in utero TCDD exposure in order to examine the impact of this toxicant on adult reproductive function. Our initial in utero toxicant-exposure study revealed a dose-dependent reduction in uterine sensitivity to progesterone; however, we did not previously ...

  1. Aryl Hydrocarbon Receptor Activation by TCDD Reduces Inflammation Associated with Crohn's Disease

    OpenAIRE

    Benson, Jenna M.; Shepherd, David M.

    2010-01-01

    Crohn's disease results from a combination of genetic and environmental factors that trigger an inappropriate immune response to commensal gut bacteria. The aryl hydrocarbon receptor (AhR) is well known for its involvement in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant that affects people primarily through the diet. Recently, TCDD was shown to suppress immune responses by generating regulatory T cells (Tregs). We hypothesized that AhR activation da...

  2. Vascular tissue is the first site of damage in the TCDD-exposed fish embryo

    Energy Technology Data Exchange (ETDEWEB)

    Cantrell, S.; Tillitt, D. [Midwest Science Center, Columbia, MO (United States); Hannink, M. [Univ. of Missouri, Columbia, MO (United States). Biochemistry Dept.

    1995-12-31

    The planar halogenated hydrocarbons (PHHs) are a group of environmental contaminants that exert adverse biological effects in most vertebrate organisms. Embryonic development is the most sensitive life stage to the effects of these compounds. The reason for the enhanced sensitivity to PHHs during early life stages is unknown. To study TCDD-induced embryotoxicity, a fish species the medaka was the organism of choice. The authors localized the initial site of tissue damage in the developing embryo and investigated the mechanism of TCDD-induced tissue damage. There were three parts to this study, (1) observation of morphological anomalies in the TCDD-treated embryo, (2) immunohistochemical detection of DNA damage in the tissues of TCDD-treated embryos, and (3) test the ability of an antioxidant to delay the onset of initial tissue damage. Morphological observations show that the first visual lesions that occur in the TCDD treated embryo occur at stage 36, about day 6 post fertilization. The lesions are localized in the cardiac vasculature. Immunohistochemical staining, using the terminal nucleotide transferase assay (TdT-assay) which detects DNA damage showed that the initial site of tissue damage was in the vasculature in the cardiac region. Tissue damage was detected in neural tissue and muscle tissue at later time points. TCDD is known to induce oxidative stress in a variety of organisms, therefore; the authors tested to see if oxidative stress may play a role in TCDD-induced embryotoxicity. The TCDD-treated embryos were cultured in the antioxidant N-acetyl cysteine (NAC) and the morphological observations and TdT-assay were repeated. They found that NAC was able to delay the onset of tissue damage and NAC was able to reduce total mortality in the embryo. The results from this study indicate that the cardiac vasculature is the initial site of tissue damage.

  3. Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs.

    Science.gov (United States)

    Ma, Jing; Chen, Xi; Liu, Yanan; Xie, Qunhui; Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan; Zhao, Bin; Tang, Naijun

    2015-12-01

    Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8-14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue.

  4. Genetical studies on dieldrin-resistance in Aëdes aegypti and its cross-resistance to DDT

    Science.gov (United States)

    Khan, N. H.; Brown, A. W. A.

    1961-01-01

    A strain of Aëdes aegypti was recently found in Puerto Rico which proved to be resistant to both DDT and dieldrin. This paper reports on genetical studies of this strain to determine whether a single entity is involved or two distinct resistances. Tests carried out by repeated back-crossing combined with selection pressure from DDT and dieldrin and by crossing with a strain with marker genes indicate that a single entity is responsible (dieldrin-resistance with cross-resistance to DDT) and that its genetic factor is located on chromosome 2 at a distance of 25 from locus ”yellow”. PMID:13755610

  5. Aqueous phase partitioning of hexachlorocyclohexane (HCH) isomers by biosurfactant produced by Pseudomonas aeruginosa WH-2

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Suman; Singh, Partapbir [Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, Punjab (India); Raj, Mayil [MTCC, IMTECH, Sector 39-A, Chandigarh 160036 (India); Chadha, Bhupinder Singh [Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, Punjab (India); Saini, Harvinder Singh, E-mail: sainihs@yahoo.com [Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, Punjab (India)

    2009-11-15

    The different isomers of technical-grade hexachlorocyclohexane (t-HCH) including the insecticidal {gamma}-isomer, commonly known as lindane, have been reported to be toxic, carcinogenic and endocrine disrupters. The spatial arrangements of the chlorine atoms on different isomers and low aqueous phase solubility contribute to their persistence in environment, {beta}-HCH being the most resistance to transformation. The biosurfactant preparation of Pseudomonas aeruginosa isolate WH-2 was evaluated for its ability to improve the aqueous phase partitioning of different isomers of HCH-muck. Further, the ability of biosurfactant preparation to emulsify HCH and n-hexadecane was checked under different conditions, usually characteristic of sites contaminated with pollutants viz. wide range of pH, temperature, and salinity. The data obtained from this study will be helpful in designing suitable bioremediation strategies for huge stock piles of HCH-muck and sites polluted by reckless use/disposal of HCH-isomers.

  6. Determination of Hexachlorocyclohexane by Gas Chromatography Combined with Femtosecond Laser Ionization Mass Spectrometry

    Science.gov (United States)

    Yang, Xixiang; Imasaka, Tomoko; Li, Adan; Imasaka, Totaro

    2016-09-01

    Structural isomers and enantiomers of hexachlorocyclohexane (HCH) were separated using a chiral column by gas chromatography and quantitatively determined by multiphoton ionization mass spectrometry using an ultraviolet femtosecond laser (200 and 267 nm) as the ionization source. The order of elution of the enantiomers (i.e., (+)-α-HCH and (-)-α-HCH) was predicted from stabilization energies calculated for the complexes using permethylated γ-cyclodextrin as the stationary phase of the column, and the results were compared with the experimental data. The molecular ions observed for HCH were weak, even though they can be ionized through a process of resonance enhanced two-photon ionization at 200 nm. This unfavorable result can be attributed to the dissociation of the molecular ion, as predicted from quantum chemical calculations.

  7. Use of {gamma}-hexachlorocyclohexane as a terminal electron acceptor by an anaerobic enrichment culture

    Energy Technology Data Exchange (ETDEWEB)

    Elango, Vijai, E-mail: velango@g.clemson.edu [Hazardous Substance Research Center/South and Southwest, Louisiana State University, 3221 Patrick Taylor Hall, Baton Rouge, LA 70803 (United States); Kurtz, Harry D. [Department of Genetics and Biochemistry, Clemson University, 100 Jordan Hall, Clemson, SC 29634 (United States); Anderson, Christina; Freedman, David L. [Department of Environmental Engineering and Earth Sciences, Box 340919, Clemson University, Clemson, SC 29634-0919 (United States)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer Use of {gamma}-hexachlorocyclohexane as a terminal electron acceptor was demonstrated. Black-Right-Pointing-Pointer H{sub 2} served as the electron donor for an enrichment culture that dechlorinated {gamma}-HCH. Black-Right-Pointing-Pointer H{sub 2} consumption for acetogenesis and methanogenesis stopped in HEPES media. Black-Right-Pointing-Pointer Addition of vancomycin significantly slowed the rate of {gamma}-HCH dechlorination. Black-Right-Pointing-Pointer Previously identified chlororespiring microbes were not detected in the enrichment. - Abstract: The use of {gamma}-hexachlorocyclohexane (HCH) as a terminal electron acceptor via organohalide respiration was demonstrated for the first time with an enrichment culture grown in a sulfate-free HEPES-buffered anaerobic mineral salts medium. The enrichment culture was initially developed with soil and groundwater from an industrial site contaminated with HCH isomers, chlorinated benzenes, and chlorinated ethenes. When hydrogen served as the electron donor, 79-90% of the electron equivalents from hydrogen were used by the enrichment culture for reductive dechlorination of the {gamma}-HCH, which was provided at a saturation concentration of approximately 10 mg/L. Benzene and chlorobenzene were the only volatile transformation products detected, accounting for 25% and 75% of the {gamma}-HCH consumed (on a molar basis), respectively. The enrichment culture remained active with only hydrogen as the electron donor and {gamma}-HCH as the electron acceptor through several transfers to fresh mineral salts medium for more than one year. Addition of vancomycin to the culture significantly slowed the rate of {gamma}-HCH dechlorination, suggesting that a Gram-positive organism is responsible for the reduction of {gamma}-HCH. Analysis of the {gamma}-HCH dechlorinating enrichment culture did not detect any known chlororespiring genera, including Dehalobacter. In bicarbonate-buffered medium

  8. TCDD promoted EMT of hFPECs via AhR, which involved the activation of EGFR/ERK signaling.

    Science.gov (United States)

    Gao, Zhan; Bu, Yongjun; Liu, Xiaozhuan; Wang, Xugang; Zhang, Guofu; Wang, Erhui; Ding, Shibin; Liu, Yongfeng; Shi, Ruling; Li, Qiaoyun; Fu, Jianhong; Yu, Zengli

    2016-05-01

    One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin and cytokeratin14) and enhanced the mesenchymal markers (vimentin and fibronectin), but had no effect on cell migration and apoptosis. TCDD exposure led to a dose-dependent increase in Slug protein expression. Coimmunoprecipitation revealed that TCDD promoted AhR to form a protein complex with Slug. ChIP assay confirmed that TCDD exposure recruited AhR to the xenobiotic responsive element of Slug promoter. Knockdown of AhR by siRNA remarkably weakened TCDD-induced binding of AhR to the XRE promoter of slug, thereby suppressed TCDD-induced vimentin. Further experiment showed that TCDD stimulated EGFR phosphorylation did not influence the TGFβ3/Smad signaling; whereas TCDD increased phosphorylation of ERK1/2 and p38 with no effect on activation of JNK. By using varieties of inhibitors, we confirmed that TCDD promoted proliferation and EMT of hFPECs via activation of EGFR/ERK pathway. These data make a novel contribution to the molecular mechanism of cleft palate by TCDD.

  9. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic stellate cell activation.

    Science.gov (United States)

    Harvey, Wendy A; Jurgensen, Kimberly; Pu, Xinzhu; Lamb, Cheri L; Cornell, Kenneth A; Clark, Reilly J; Klocke, Carolyn; Mitchell, Kristen A

    2016-02-17

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, gross markers of TCDD toxicity are attributed to AhR activation in parenchymal hepatocytes. However, less is known regarding the consequences of TCDD treatment on non-parenchymal cells in the liver. Hepatic stellate cells (HSCs) are non-parenchymal cells that store vitamin A when quiescent. Upon liver injury, activated HSCs lose this storage ability and instead function in the development and maintenance of inflammation and fibrosis through the production of pro-inflammatory mediators and collagen type I. Reports that TCDD exposure disrupts hepatic retinoid homeostasis and dysregulates extracellular matrix remodeling in the liver led us to speculate that TCDD treatment may disrupt HSC activity. The human HSC line LX-2 was used to test the hypothesis that TCDD treatment directly activates HSCs. Results indicate that exposure to 10nM TCDD almost completely inhibited lipid droplet storage in LX-2 cells cultured with retinol and palmitic acid. TCDD treatment also increased LX-2 cell proliferation, expression of α-smooth muscle actin, and production of monocyte chemoattractant protein-1 (MCP-1), all of which are characteristics of activated HSCs. However, TCDD treatment had no effect on Col1a1 mRNA levels in LX-2 cells stimulated with the potent profibrogenic mediator, transforming growth factor-β. The TCDD-mediated increase in LX-2 cell proliferation, but not MCP-1 production, was abolished when phosphoinositide 3-kinase was inhibited. These results indicate that HSCs are susceptible to direct modulation by TCDD and that TCDD likely increases HSC activation through a multi-faceted mechanism.

  10. 2, 3, 7, 8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    OpenAIRE

    Fullerton, Aaron M.; Roth, Robert A.; Ganey, Patricia E.

    2012-01-01

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30µg/kg TCDD or vehicle cont...

  11. Carrying-over toxicokinetic model uncertainty into cancer risk estimates. The TCDD example

    Energy Technology Data Exchange (ETDEWEB)

    Edler, L. [Division of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Heinzl, H.; Mittlboeck, M. [Medical Univ. of Vienna (Austria). Dept. of Medical Computer Sciences

    2004-09-15

    Estimation of human cancer risks depends on the assessment of exposure to the investigated hazardous compound as well as on its toxicokinetic and toxicodynamic in the body. Modeling these processes constitutes a basic prerequisite for any quantitative risk assessment including assessment of the uncertainty of risk estimates. Obviously, the modeling process itself is part of the risk assessment task, and it affects the development of valid risk estimates. Due to the wealth of information available on exposure and effects in humans and animals 2,3,7,8 tetrachlorodibenzo-pdioxin (TCDD) provides an excellent example to elaborate methods which allow a quantitative analysis of the uncertainty of TCDD risk estimates, and which show how toxicokinetic model uncertainty carries over to risk estimate uncertainty and uncertainty of the dose-response relationship. Cancer is usually considered as a slowly evolving disease. An increase in TCDD dose may result in an increase of the observable cancer response not until some latency time period has elapsed. This fact needs careful consideration when a dose-response relationship is to be established. Toxicokinetic models are capable to reconstruct TCDD exposure concentrations during a lifetime such that time-dependent TCDD dose metrics like the area under the concentration-time curve (AUC) can be constructed for each individual cohort member. Two potentially crucial model assumptions for estimating the exposure of a person are the assumption of lifetime constancy of total lipid volume (TLV) of the human body and the assumption of a simple linear kinetic of TCDD elimination. In 1995 a modified Michaelis-Menten kinetic (also known as Carrier kinetic) has been suggested to link the TCDD elimination rate to the available TCDD amount in the body. That is, TCDD elimination would be faster, of nearly the same rate, or slower under this kinetic than under a simple linear kinetic when the individual would be highly, moderately, or slightly

  12. TCDD induces the hypoxia-inducible factor (HIF)-1α regulatory pathway in human trophoblastic JAR cells.

    Science.gov (United States)

    Liao, Tien-Ling; Chen, Su-Chee; Tzeng, Chii-Reuy; Kao, Shu-Huei

    2014-09-30

    The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α) stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS) and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor) or N-acetylcysteine (a ROS scavenger). The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  13. Protective effects of protocatechuic acid on TCDD-induced oxidative and histopathological damage in the heart tissue of rats.

    Science.gov (United States)

    Ciftci, Osman; Disli, Olcay Murat; Timurkaan, Necati

    2013-10-01

    2,3,7,8-Tetracholorodibenzo-p-dioxin (TCDD) is a highly toxic environmental contaminant that causes severe toxic effects in animal and human. In this study, we investigated the toxic effects of TCDD and the preventive effects of protocatechuic acid (PCA), a widespread phenolic compound, in the heart tissue of rats. For this purpose, 3-4 months old 28 rats with 280-310 g body weights were equally divided into 4 groups (control, TCDD, PCA, TCDD + PCA group). A 2 μg/kg dose of 2,3,7,8-TCDD and 100 mg/kg dose of PCA were dissolved in corn oil and given orally to the rats for 45 days. The results indicated that TCDD induced oxidative stress by increasing the level of thiobarbituric acid reactive substance and by decreasing the levels of glutathione, catalase, glutathione peroxidase and superoxide dismutase in the heart tissue of rats. In contrast, PCA treatment prevents the toxic effects of TCDD on oxidative stress. In addition, histopathological alterations such as necrosis and hemorrhage occurred in TCDD group, and PCA treatment partially prevents these alterations in heart tissue. In this study, it was concluded that TCDD exposure led to toxic effects in heart tissue and PCA treatment could prevent the toxicity of TCDD.

  14. TCDD Promotes Lung Tumors via Attenuation of Apoptosis through Activation of the Akt and ERK1/2 Signaling Pathways

    OpenAIRE

    2014-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant...

  15. Serum metabolomic pertubations among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Saberi Hosnijeh, Fatemeh; Pechlivanis, Alexandros; Keun, Hector C; Portengen, Lützen; Bueno-de-Mesquita, H Bas; Heederik, Dick; Vermeulen, Roel

    2013-08-01

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with multiple health effects. Mechanistic studies using metabolomics could provide supporting evidence for such associations by identifying relevant biological pathways. In this study, we investigated metabolic perturbations in a cohort of TCDD exposed workers to better understand TCDD related health effects. Eighty one workers who had been exposed to TCDD in the past and 63 nonexposed workers were included in the study. Serum metabolites were detected using ultra high pressure liquid chromatography coupled online to a Q-TOF Premier mass spectrometer with a scan range of 70-1,000 m/z. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high resolution mass spectrometry. TCDD blood levels at the time of last exposure were estimated using a one-compartment first order kinetic model. Differentially expressed metabolites were identified using linear regression models, partial least squares regression (PLSr) and a regression-based Bayesian variable selection approach. Features that were present in all quality control samples and had a coefficient of variation 0.05). PLSr analyses and Bayesian variable selection regression analyses revealed no obvious metabolic perturbations associated with TCDD levels. This is the first metabolomic analysis related to TCDD exposure in humans. No significant metabolic features were identified. It is concluded that TCDD exposure at levels present in this study does not lead to significant perturbations of the serum metabolome.

  16. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Fullerton, Aaron M., E-mail: fuller22@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, 1129 Farm Lane, Room 215, East Lansing, MI 48824 (United States); Roth, Robert A., E-mail: rothr@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 221, East Lansing, MI 48824 (United States); Ganey, Patricia E., E-mail: ganey@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 214, East Lansing, MI 48824 (United States)

    2013-01-15

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  17. Organochlorine insecticides lindane and dieldrin and their binary mixture disturb calcium homeostasis in dopaminergic PC12 cells

    NARCIS (Netherlands)

    Heusinkveld, H.J.|info:eu-repo/dai/nl/305960385; Westerink, R.H.S.|info:eu-repo/dai/nl/239425952

    2012-01-01

    Current hypotheses link long-term environmental exposure of humans to persistent organochlorine (OC) insecticides lindane (HCH) and dieldrin (HEOD) to the development of neurodegenerative disorders, such as Parkinson's disease. Primary adverse neurological effects of these insecticides are directed

  18. TOXICOKINETIC INTERACTIONS AND SURVIVAL OF HYALELLA AZTECA EXPOSED TO BINARY MIXTURES OF CHLORPYRIFOS, DIELDRIN, AND METHYL MERCURY

    Science.gov (United States)

    Chemical mixture interactions of chlorpyrifos, dieldrin, and methyl mercury were evaluated in Hyalella azteca. Survival of adult and juvenile organisms was evaluated following exposure to individual chemicals and in binary combinations. Binary interactions of the model chemicals...

  19. Schadelijke effecten van Dieldrin op voortplanting en nageslacht, anders dan via de inwerking op het erfelijk materiaal : een literatuurstudie

    NARCIS (Netherlands)

    Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.L.

    1989-01-01

    Literatuuronderzoek naar de schadelijke effecten van Dieldrin op voortplanting en nageslacht. Dierproefgegevens en humane gegevens worden geevalueerd. Aandacht wordt besteed aan blootstelling, effecten t.a.v. zwangerschap en nageslacht, effecten t.a.v. de geslachtsorganen, endocrien systeem en

  20. Modulatory Influence of Segmented Filamentous Bacteria on Transcriptomic Response of Gnotobiotic Mice Exposed to TCDD

    Directory of Open Access Journals (Sweden)

    Robert D. Stedtfeld

    2017-09-01

    Full Text Available Environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an aryl hydrocarbon receptor (AhR, are known to induce host toxicity and structural shifts in the gut microbiota. Key bacterial populations with similar or opposing functional responses to AhR ligand exposure may potentially help regulate expression of genes associated with immune dysfunction. To examine this question and the mechanisms for AhR ligand-induced bacterial shifts, C57BL/6 gnotobiotic mice were colonized with and without segmented filamentous bacteria (SFB – an immune activator. Mice were also colonized with polysaccharide A producing Bacteroides fragilis – an immune suppressor to serve as a commensal background. Following colonization, mice were administered TCDD (30 μg/kg every 4 days for 28 days by oral gavage. Quantified with the nCounter® mouse immunology panel, opposing responses in ileal gene expression (e.g., genes associated with T-cell differentiation via the class II major histocompatibility complex as a result of TCDD dosing and SFB colonization were observed. Genes that responded to TCDD in the presence of SFB did not show a significant response in the absence of SFB, and vice versa. Regulatory T-cells examined in the mesenteric lymph-nodes, spleen, and blood were also less impacted by TCDD in mice colonized with SFB. TCDD-induced shifts in abundance of SFB and B. fragilis compared with previous studies in mice with a traditional gut microbiome. With regard to the mouse model colonized with individual populations, results indicate that TCDD-induced host response was significantly modulated by the presence of SFB in the gut microbiome, providing insight into therapeutic potential between AhR ligands and key commensals.

  1. Dieldrin Augments mTOR Signaling and Regulates Genes Associated with Cardiovascular Disease in the Adult Zebrafish Heart (Danio rerio).

    Science.gov (United States)

    Slade, Logan; Cowie, Andrew; Martyniuk, Chris J; Kienesberger, Petra C; Pulinilkunnil, Thomas

    2017-06-01

    Dieldrin is a legacy organochlorine pesticide that is persistent in the environment, despite being discontinued from use in North America since the 1970s. Some epidemiologic studies suggest that exposure to dieldrin is associated with increased risks of neurodegenerative disease and breast cancer by inducing inflammatory responses in tissues as well as oxidative stress. However, the direct effects of organochlorine pesticides on the heart have not been adequately addressed to date given that these chemicals are detectable in human serum and are environmentally persistent; thus, individuals may show latent adverse effects in the cardiovascular system due to long-term, low-dose exposure over time. Our objective was to determine whether low-level exposure to dieldrin at an environmentally relevant dose results in aberrant molecular signaling in the vertebrate heart. Using transcriptomic profiling and immunoblotting, we determined the global gene and targeted protein expression response to dieldrin treatment and show that dieldrin affects gene networks in the heart that are associated with processes related to cardiovascular disease, specifically cardiac arrest and ventricular fibrillation. We report that genes regulating inflammatory responses, a significant risk factor for cardiovascular disease, are upregulated by dieldrin whereas transcripts related to lysosomal function are significantly downregulated. To verify these findings, proteins in these pathways were examined with immunoblotting, and our results demonstrate that dieldrin constitutively activates Akt/mTOR signaling and downregulates lysosomal genes, participating in autophagy. Our data demonstrate that dieldrin induces genes associated with cardiovascular dysfunction and compromised lysosomal physiology, thereby identifying a novel mechanism for pesticide-induced cardiotoxicity. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Allopregnanolone prevents dieldrin-induced NMDA receptor internalization and neurotoxicity by preserving GABA(A) receptor function.

    Science.gov (United States)

    Briz, Víctor; Parkash, Jyoti; Sánchez-Redondo, Sara; Prevot, Vincent; Suñol, Cristina

    2012-02-01

    Dieldrin is an endocrine disruptor that accumulates in mammalian adipose tissue and brain. It induces convulsions due to its antagonism of the γ-aminobutyric acid A receptor (GABA(A)R). We have previously reported that long-term exposure to dieldrin causes the internalization of the N-methyl-D-aspartate receptor (NMDAR) as a result of persistent GABA(A)R inhibition. Because the neurosteroids 17β-estradiol (E2) and allopregnanolone are known to modulate the function and trafficking of GABA(A)R and NMDAR, we examined the effects of E2 and allopregnanolone on dieldrin-induced GABA(A)R inhibition, NMDAR internalization, and neuronal death in cortical neurons. We found that 1 nM E2 increased the membrane expression of NR1/NR2B receptors and postsynaptic density 95 but did not induce their physical association. In contrast, 10 nM E2 had no effect on these proteins but reduced NR2A membrane expression. We also found that exposure to 60 nM dieldrin for 6 d in vitro caused the internalization of NR1 and NR2B but not NR2A. Treatment with either 1 nM E2 or 10 μM allopregnanolone prevented the dieldrin-induced reduction in membrane levels of the NR1/NR2B receptors. Furthermore, prolonged exposure to 200 nM dieldrin down-regulated the expression of NR2A; this was inhibited only by allopregnanolone. Although both hormones restored NMDAR function, as measured by the NMDA-induced rise in intracellular calcium, allopregnanolone (but not E2) reversed the inhibition of GABA(A)R and neuronal death caused by prolonged exposure to dieldrin. Our results indicate that allopregnanolone protects cortical neurons against the neurotoxicity caused by long-term exposure to dieldrin by maintaining GABA(A)R and NMDAR functionality.

  3. Reduction of glutamatergic neurotransmission by prolonged exposure to dieldrin involves NMDA receptor internalization and metabotropic glutamate receptor 5 downregulation.

    Science.gov (United States)

    Briz, Victor; Galofré, Mireia; Suñol, Cristina

    2010-01-01

    Dieldrin was previously used as a pesticide. Although its use has been discontinued, humans are still exposed to it due to its high environmental persistence and because it accumulates in the adipose tissue of animals. Acute exposure to dieldrin provokes convulsions due to its antagonism on the gamma-aminobutyric acid-A (GABA(A)) receptor. However, little is known about the effects of low chronic exposure to this pollutant. In the present work, we use primary cultures of cortical neurons to study the mechanisms involved in the toxic action of dieldrin. We found that 2 and 6 days in vitro (DIV) exposure to a subcytotoxic concentration (60nM) of dieldrin reduced the increase in intracellular calcium concentration ([Ca(2+)](i)) and the excitotoxicity caused by glutamate. Exposure to dieldrin for 6 DIV induced N-methyl-D-aspartate receptor (NMDAR) internalization and reduced metabotropic glutamate receptor 5 (mGLUR5) levels. Double immunostaining for NMDAR and mGLUR5 showed that these receptors lose colocalization on the cell membrane in neurons treated with dieldrin. No changes were observed in receptor functionalities or receptor levels after 2 DIV of exposure to dieldrin. However, the increase in [Ca(2+)](i) induced by coactivation of NMDAR and mGLUR5 was significantly reduced. Thus, a functional interaction between the two receptors seems to play an important role in glutamate-induced excitotoxicity. We confirm that permanent blockade of the GABA(A) receptor by this persistent pesticide triggers adaptive neuronal changes consisting of a reduction of glutamatergic neurotransmission. This might explain the cognitive and learning deficits observed in animals after chronic treatment with dieldrin.

  4. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury.

    Science.gov (United States)

    Fullerton, Aaron M; Roth, Robert A; Ganey, Patricia E

    2013-01-15

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4-10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell-cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression.

  5. Influence of activated charcoal amendment to contaminated soil on dieldrin and nutrient uptake by cucumbers.

    Science.gov (United States)

    Hilber, Isabel; Wyss, Gabriela S; Mäder, Paul; Bucheli, Thomas D; Meier, Isabel; Vogt, Lea; Schulin, Rainer

    2009-01-01

    Activated charcoal (AC) amendments have been suggested as a promising, cost-effective method to immobilize organic contaminants in soil. We performed pot experiments over two years with cucumber (Cucumis sativus L.) grown in agricultural soil with 0.07 mg kg(-1) of weathered dieldrin and 0, 200, 400, and 800 mg AC per kg soil. Dieldrin fresh weight concentrations in cucumber fruits were significantly reduced from 0.012 to an average of 0.004 mg kg(-1), and total uptake from 2 to 1 microg in the 800 mg kg(-1) AC treatment compared to the untreated soil. The treatment effects differed considerably between the two years, due to different meteorological conditions. AC soil treatments did neither affect the availability of nutrients to the cucumber plants nor their yield (total fruit wet weight per pot). Thus, some important prerequisites for the successful application of AC amendments to immobilize organic pollutants in agricultural soils can be considered fulfilled.

  6. Synergistic microglial reactive oxygen species generation induced by pesticides lindane and dieldrin.

    Science.gov (United States)

    Mao, Haoyu; Liu, Bin

    2008-08-27

    Elevated environmental exposure to pesticides is a known risk factor to the development of sporadic Parkinson's disease resulting from the degeneration of nigral dopamine neurons. Among the suspected agents are the highly persistent and bioaccumulative organochlorinated pesticides (OCPs). We report here that lindane and dieldrin, two widely present OCPs that are found enriched in the nigra of postmortem Parkinson's disease brains synergistically induced the production of reactive oxygen species (ROS) in microglia. Inhibitor studies indicated that the lindane and dieldrin-induced ROS generation was mediated by NADPH oxidase. As microglial ROS is a key contributor to the degeneration of the oxidative damage-vulnerable dopamine neurons, our findings shed significant light on the role of OCPs in the development of Parkinson's disease.

  7. [Ambient pressure synthesis and characterization of silica aerogel as adsorbent for dieldrin].

    Science.gov (United States)

    Sha, Wei; Liu, Rui-ping; Liu, Hui-juan; Qu, Jiu-hui

    2008-12-01

    Hydrophobic silica aerogels were prepared from cheap waterglass precursors via surface modification of wet gels and ambient pressure drying route. Its adsorption capacity of Dieldrin, a typical of persistent organic pollutants (POPs), was examined. It is characterized via BET, FTIR, and DSC-TGA. The silica aerogels were highly hydrophobic with contact angles of 135 degrees-142 degrees, and the hydrophobicity of the aerogels could be maintained up to the temperature of 380 degrees C. The silica aerogels were porous with, pore size distribution of 17.5-23.4 nm, porosity of 94.8%-95.6%, and surface area of 444-560 m2 x g(-1). The results of adsorption experiments indicated that the hydrophobic aerogels could remove 84% of dieldrin from aqueous solution within 4 h; the adsorption process followed the pseudo-second-order kinetics process. Based on the adsorption equilibrium results, the adsorption capacity of silica aerogel was 11 times bigger than by active carbon.

  8. Photochemical Activity of Aldrin and Dieldrin in Liquid and Frozen Aqueous Systems: Field and Laboratory Studies

    Science.gov (United States)

    Bausch, A. R.; Rowland, G. A.; Grannas, A. M.

    2008-12-01

    The phenomenon of global distillation generates significant accumulation of volatile, anthropogenic persistent organic pollutants (POPs) in polar regions. Bioaccumulation presents serious concerns for human health within Arctic subsistence communities. In the recent past, the photochemical processes of POPs have been observed in the laboratory. Despite some established knowledge regarding photochemical processes in reactive frozen media, little published literature exists regarding the chemical transformations and fate of POPs in the Arctic. Here, we consider the photochemical transformations of aldrin and dieldrin, two structurally similar organochlorine pollutants whose presence has been confirmed in the Arctic. Their photochemical transformation, resulting from ultraviolet exposure, was investigated by both field studies in Barrow, AK and controlled laboratory experiments. Pollutant degradation and photoproduct formation were monitored by GC-ECD analysis. Based on kinetic studies of liquid and frozen samples and identification of photoproducts, we will propose potential reaction mechanisms for the transformations of aldrin and dieldrin. Further implications for environmental processes will be discussed.

  9. Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems.

    Science.gov (United States)

    Prokopec, Stephenie D; Houlahan, Kathleen E; Sun, Ren X; Watson, John D; Yao, Cindy Q; Lee, Jamie; P'ng, Christine; Pang, Renee; Wu, Alexander H; Chong, Lauren C; Smith, Ashley B; Harding, Nicholas J; Moffat, Ivy D; Lindén, Jere; Lensu, Sanna; Okey, Allan B; Pohjanvirta, Raimo; Boutros, Paul C

    2017-01-13

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptional effects of ligand-activated AHR. Specifically, we have created a datasets package - TCDD.Transcriptomics - for the R statistical environment, consisting of 63 unique experiments comprising 377 samples, including various combinations of 3 species (human derived cell lines, mouse and rat), 4 tissue types (liver, kidney, white adipose tissue and hypothalamus) and a wide range of TCDD exposure times and doses. These datasets have been fully standardized using consistent preprocessing and annotation packages (available as of September 14, 2015). To demonstrate the utility of this R package, a subset of "AHR-core" genes were evaluated across the included datasets. Ahrr, Nqo1 and members of the Cyp family were significantly induced following exposure to TCDD across the studies as expected while Aldh3a1 was induced specifically in rat liver. Inmt was altered only in liver tissue and primarily by rat-AHR. Analysis of the "AHR-core" genes demonstrates a continued need for studies surrounding the impact of AHR-activity on the transcriptome; genes believed to be consistently regulated by ligand-activated AHR show surprisingly little overlap across species and tissues. Until now, a comprehensive assessment of the transcriptome across these studies was challenging due to differences in array platforms

  10. Relative potency of PCB126 to TCDD for sublethal embryotoxicity in the mummichog (Fundulus heteroclitus).

    Science.gov (United States)

    Rigaud, Cyril; Couillard, Catherine M; Pellerin, Jocelyne; Légaré, Benoît; Gonzalez, Patrice; Hodson, Peter V

    2013-03-15

    The relative potency (ReP) of 3,3',4,4',5-pentachlorobiphenyl (PCB126) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for sublethal responses was assessed in Fundulus heteroclitus embryos. Eggs were treated with intravitelline injections of graded sublethal doses of PCB126 (312-5000 pg g(-1) wet weight, ww) or TCDD (5-1280 pg g(-1) ww). At 16 days post-fertilization (DPF), craniofacial deformities were observed in larvae hatched from eggs treated with the two highest doses of PCB126 (2500-5000 pg g(-1) ww). Both compounds caused a dose-responsive reduction of larval growth and prey capture ability (at ≥1250 pg g(-1) ww), and induction of ethoxyresorufin-O-deethylase (EROD) activity (at ≥80 pg g(-1) ww). The dose-response relationships for EROD activity for PCB126 and TCDD had similar slopes and the ReP of PCB126 to TCDD for EROD activity was estimated at 0.71. This is 140-fold higher than the World Health Organization (WHO) TCDD equivalency factor (TEF) of PCB126 for fish (0.005), which is based on rainbow trout (Oncorhynchus mykiss) embryolethality data. The slope of the dose-response relationship for prey capture ability for PCB126 was steeper than for TCDD, suggesting different mechanisms of action. Expression levels of several genes were also studied by quantitative real-time polymerase chain reaction (qPCR) following exposure to single doses of TCDD or PCB126 (1280 and 1250 pg g(-1) ww, respectively) causing similar EROD induction. A different pattern of responses was observed between PCB126 and TCDD: PCB126 appeared to induce antioxidant responses by inducing sod2 expression, while TCDD did not. These results suggest that relative potencies are species-specific and that the current ReP for PCB126 underestimates its toxicity for some fish species. It is recommended to develop species-specific RePs for a variety of sublethal endpoints and at environmentally relevant doses.

  11. Photochemical processing of aldrin and dieldrin in frozen aqueous solutions under arctic field conditions

    Energy Technology Data Exchange (ETDEWEB)

    Rowland, Glenn A.; Bausch, Alexandra R. [Department of Chemistry, Villanova University, Villanova, PA 19085 (United States); Grannas, Amanda M., E-mail: amanda.grannas@villanova.edu [Department of Chemistry, Villanova University, Villanova, PA 19085 (United States)

    2011-05-15

    Organochlorine (OC) contaminants are transported to the Polar Regions, where they have the potential to bioaccumulate, presenting a threat to the health of wildlife and indigenous communities. They deposit onto snowpack during winter, and accumulate until spring, when they experience prolonged solar irradiation until snowmelt occurs. Photochemical degradation rates for aldrin and dieldrin, in frozen aqueous solution made from MilliQ water, 500 {mu}M hydrogen peroxide solution or locally-collected melted snow were measured in a field campaign near Barrow, AK, during spring-summer 2008. Significant photoprocessing of both pesticides occurs; the reactions depend on temperature, depth within the snowpack and whether the predominant phase is ice or liquid water. The effect of species present in natural snowpack is comparable to 500 {mu}M hydrogen peroxide, pointing to the potential significance of snowpack-mediated reactions. Aldrin samples frozen at near 0 deg. C were more reactive than comparable liquid samples, implying that the microenvironments experienced on frozen ice surfaces are an important consideration. - Highlights: > Photodegradation rates for aldrin and dieldrin in frozen aqueous solutions made from MilliQ water, H{sub 2}O{sub 2} or melted snow are reported. > Photoprocessing depends on temperature, depth beneath the snowpack surface and dominant phase. > Species present in natural snowpack have a photosensitizing effect comparable to 500 {mu}M H{sub 2}O{sub 2}. > Aldrin samples frozen at near 0 deg. C were more reactive than comparable liquid samples. > Collectively we find that frozen aqueous surfaces play a unique role in aldrin and dieldrin photochemistry. - A field study finds that frozen aqueous solutions of aldrin and dieldrin undergo photochemical degradation under arctic snowpack conditions. The reactions are enhanced in frozen systems and by natural snowpack constituents.

  12. Dopamine and norepinephrine depletion in ring doves fed DDE, dieldrin, and Aroclor 1254

    Science.gov (United States)

    Heinz, G.H.; Hill, E.F.; Contrera, J.F.

    1980-01-01

    The levels of dopamine and norepinephrine were measured in one-half of the brain of ring doves fed a control diet or a diet containing 2, 20, or 200 ppm DDE; 1, 4, or 16 ppm dieldrin; or 1, 10, or 100 ppm Aroclor 1254. Levels of DDE, dieldrin, or Aroclor 1254 were determined in the other half of each brain. The intermediate and high levels of each chemical caused depletions in both neurotransmitters, and brain residues of each chemical were negatively correlated with levels of neurotransmitters. The highest concentrations of DDE, dieldrin, and Aroclor 1254 depressed averages of dopamine to 42.4, 41.4, and 45.2% of the control level and norepinephrine to 61.6, 62.0, and 56.9% of controls, respectively. Depletions of dopamine and norepinephrine could result in abnormal behavior of contaminated birds in the wild, and the detection of such depletions could become an important tool in assessing contaminant-induced behavioral aberrations in birds.

  13. Persistence and changes in bioavailability of dieldrin, DDE and heptachlor epoxide in earthworms over 45 years

    Science.gov (United States)

    Beyer, W. Nelson; Gale, Robert W.

    2013-01-01

    The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

  14. Field Performance of Dieldrin/Resin Wettable Powders on Sorptive Mud Surface

    Science.gov (United States)

    Van Tiel, N.

    1961-01-01

    Recent field experiments on the relative performance of dieldrin and dieldrin/resin wettable powders on sorptive mud surface have not confirmed the promising results obtained with the latter products in earlier laboratory tests. In view of this a renewed investigation into the possible factors governing the performance of such products was considered desirable, and further laboratory and field experiments were carried out in co-operation with the Colonial Pesticides Research Unit at Arusha, Tanganyika. The results of these experiments have given a better understanding of the factors involved, and a coherent interpretation of the differences in performance shown by various products under different conditions. The main factors to be taken into account appear to be: mobility of the insects during exposure, as influenced by insect species and exposure conditions; inherent toxicity of the dieldrin/resin particles; and the average relative humidity inside the experimental huts. The sorption phenomenon can be demonstrated in the field, but in view of the humidity conditions it does not seem likely that it will interfere seriously with practical mosquito control. A potential critical condition might be prevalent only in areas where the presence of sorptive mud is coupled with long periods of low humidity inside the huts, but further experimental data are necessary to confirm this. PMID:13780061

  15. Identification of a dieldrin resistance-associated mutation in Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

    Science.gov (United States)

    Hope, Michelle; Menzies, Moira; Kemp, David

    2010-08-01

    The southern cattle tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae), is a major vector of tick fever organisms affecting cattle in many parts of the world, including Australia, Africa, and South America. Control of the southern cattle tick through acaricide use is an important approach in disease management. Resistance has emerged to many of the acaricides currently and previously used, including the cyclodienes. Although cyclodiene resistance mechanisms have been characterized in many insect species, this report is the first to identify mutations associated with dieldrin resistance in the cattle tick. A novel two base pair mutation in the GABA-gated chloride channel gene has been identified at position 868-9 and causes a codon change from threonine to leucine. Analysis of a small number of field-collected samples resistant to dieldrin shows this mutation has been maintained without selection pressure since the withdrawal of dieldrin in Australia > 20 yr ago. The mutation is not found in other laboratory-maintained strains of R. microplus that were subject to selection pressure with various acaricides.

  16. Persistence and changes in bioavailability of dieldrin, DDE, and heptachlor epoxide in earthworms over 45 years.

    Science.gov (United States)

    Beyer, W Nelson; Gale, Robert W

    2013-02-01

    The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

  17. Impact of dieldrin on liver morphological and biochemical parameters of rats.

    Science.gov (United States)

    Hallegue, Dorsaf; Tebourbi, Olfa; Kacem, Kamel; Sakly, Mohsen; Ben Rhouma, Khémaïs

    2010-04-01

    The current study deals with the effect of the organochlorine insecticide on the liver of Wistar rats. The dieldrin effect on rats was tested after a single intraperitoneal (i.p.) injection of two doses: 3 and 6 mg/kg and observations were made 4 days later. Animals showed a significant dose-dependent increase in relative liver weight. Elevations of transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]), bilirubin and total activity of lactate dehydrogenase (LDH) were recorded in the sera of treated rats. Serum LDH-5 isoenzyme activity increases in a dose-dependent manner. In contrast, LDH-1 activity does not show any significant variations with respect to controls. Histological examination of the liver of dieldrin-treated animals revealed cytoplasmic vacuolation, focal necrosis and nuclear enlargement of hepatocytes. This study suggests that biochemical assessment (transaminases, LDH and bilirubin activity) and LDH (LDH-1 & LDH-5) isoenzyme profiles can be very helpful in defining the border of the liver injury, dieldrin damaged liver would be a valuable addition to histological analysis in evaluating histopathological liver changes.

  18. Influence of activated charcoal amendment to contaminated soil on dieldrin and nutrient uptake by cucumbers

    Energy Technology Data Exchange (ETDEWEB)

    Hilber, Isabel [Research Institute of Organic Agriculture, Ackerstrasse, CH-5070 Frick (Switzerland); Wyss, Gabriela S., E-mail: gabriela.wyss@fibl.or [Research Institute of Organic Agriculture, Ackerstrasse, CH-5070 Frick (Switzerland); Maeder, Paul [Research Institute of Organic Agriculture, Ackerstrasse, CH-5070 Frick (Switzerland); Bucheli, Thomas D. [Agroscope Reckenholz-Taenikon Research Station ART, Reckenholzstr. 191, CH-8046 Zuerich (Switzerland); Meier, Isabel; Vogt, Lea; Schulin, Rainer [Institute of Terrestrial Ecosystems, ETH Zuerich, Universitaetstr. 16, CH-8092 Zuerich (Switzerland)

    2009-08-15

    Activated charcoal (AC) amendments have been suggested as a promising, cost-effective method to immobilize organic contaminants in soil. We performed pot experiments over two years with cucumber (Cucumis sativus L.) grown in agricultural soil with 0.07 mg kg{sup -1} of weathered dieldrin and 0, 200, 400, and 800 mg AC per kg soil. Dieldrin fresh weight concentrations in cucumber fruits were significantly reduced from 0.012 to an average of 0.004 mg kg{sup -1}, and total uptake from 2 to 1 mug in the 800 mg kg{sup -1} AC treatment compared to the untreated soil. The treatment effects differed considerably between the two years, due to different meteorological conditions. AC soil treatments did neither affect the availability of nutrients to the cucumber plants nor their yield (total fruit wet weight per pot). Thus, some important prerequisites for the successful application of AC amendments to immobilize organic pollutants in agricultural soils can be considered fulfilled. - The addition of activated charcoal to soil reduced dieldrin residues in cucumbers and did not affect nutrients availability.

  19. Protective effects of fenugreek (Trigonella foenum graecum L.) upon dieldrin-induced toxicity in male rat.

    Science.gov (United States)

    Hfaiedh, Najla; Alimi, Hichem; Murat, Jean-Claude; Elfeki, Abdelfattah

    2012-12-01

    The purpose of this study was to evaluate the protective effects of fenugreek (Trigonella foenum graecum L.) upon dieldrin-induced perturbations of haematological parameters and damages to liver and kidney of male Wistar rats. Under our experimental conditions, dieldrin poisoning resulted in 1) an alteration of several haematological parameters, 2) an oxidative stress evidenced by an increase of lipids peroxidation level associated with an increase of superoxide dismutase activity and a decrease of glutathione peroxidase and catalase activities in hepatic and renal tissues, 3) increased levels of glucose, total cholesterol, triglycerides, creatinine, urea, uric acid and proteins in blood, 4) increased activities of lactate dehydrogenase, alkaline phosphatase and transaminases in blood. Previous administration of fenugreek was found to hinder these dieldrin-induced damages: all hematological, renal and hepatic biomarkers, level of lipids peroxidation and activities of catalase and glutathione-peroxidase in liver and kidney were kept close to control values. This protective effect is mainly attributed to antioxidant properties of fenugreek.

  20. TCDD-induced anorexia and wasting syndrome in rats: effects of diet-induced obesity and nutrition.

    Science.gov (United States)

    Tuomisto, J T; Pohjanvirta, R; Unkila, M; Tuomisto, J

    1999-04-01

    Interactions of diet and diet-induced obesity, and the characteristic wasting syndrome caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in TCDD-resistant Han/Wistar and TCDD-sensitive Long-Evans rats. The rats were made obese by feeding them either a high-energy diet (consisting of chocolate, cheese, and chow) or force feeding. TCDD reduced body weight in a parallel manner in lean and obese rats. The high-energy diet diminished the body weight loss and increased the survival time in L-E rats after a lethal dose of TCDD, while energy supplement with high-fat/low-protein food had an opposite effect. In conclusion, diet-induced obesity and TCDD had additive effects on body weight. Dietary manipulations were able to modify the weight loss and survival time after TCDD. Fat seems to have a negative impact, while carbohydrate or protein may have a positive impact in this respect. The results are in agreement with a view that TCDD-exposed rats have a negative fat balance favoring fat loss.

  1. Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta: Implications for neurodegeneration in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Kanthasamy Anumantha G

    2008-10-01

    Full Text Available Abstract Background In previous work, we investigated dieldrin cytotoxicity and signaling cell death mechanisms in dopaminergic PC12 cells. Dieldrin has been reported to be one of the environmental factors correlated with Parkinson's disease and may selectively destroy dopaminergic neurons. Methods Here we further investigated dieldrin toxicity in a dopaminergic neuronal cell model of Parkinson's disease, namely N27 cells, using biochemical, immunochemical, and flow cytometric analyses. Results In this study, dieldrin-treated N27 cells underwent a rapid and significant increase in reactive oxygen species followed by cytochrome c release into cytosol. The cytosolic cytochrome c activated caspase-dependent apoptotic pathway and the increased caspase-3 activity was observed following a 3 hr dieldrin exposure in a dose-dependent manner. Furthermore, dieldrin caused the caspase-dependent proteolytic cleavage of protein kinase C delta (PKCδ into 41 kDa catalytic and 38 kDa regulatory subunits in N27 cells as well as in brain slices. PKCδ plays a critical role in executing the apoptotic process in dieldrin-treated dopaminergic neuronal cells because pretreatment with the PKCδ inhibitor rottlerin, or transfection and over-expression of catalytically inactive PKCδK376R, significantly attenuates dieldrin-induced DNA fragmentation and chromatin condensation. Conclusion Together, we conclude that caspase-3-dependent proteolytic activation of PKCδ is a critical event in dieldrin-induced apoptotic cell death in dopaminergic neuronal cells.

  2. Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease.

    Science.gov (United States)

    Kanthasamy, Anumantha G; Kitazawa, Masashi; Yang, Yongjie; Anantharam, Vellareddy; Kanthasamy, Arthi

    2008-10-22

    In previous work, we investigated dieldrin cytotoxicity and signaling cell death mechanisms in dopaminergic PC12 cells. Dieldrin has been reported to be one of the environmental factors correlated with Parkinson's disease and may selectively destroy dopaminergic neurons. Here we further investigated dieldrin toxicity in a dopaminergic neuronal cell model of Parkinson's disease, namely N27 cells, using biochemical, immunochemical, and flow cytometric analyses. In this study, dieldrin-treated N27 cells underwent a rapid and significant increase in reactive oxygen species followed by cytochrome c release into cytosol. The cytosolic cytochrome c activated caspase-dependent apoptotic pathway and the increased caspase-3 activity was observed following a 3 hr dieldrin exposure in a dose-dependent manner. Furthermore, dieldrin caused the caspase-dependent proteolytic cleavage of protein kinase C delta (PKCδ) into 41 kDa catalytic and 38 kDa regulatory subunits in N27 cells as well as in brain slices. PKCδ plays a critical role in executing the apoptotic process in dieldrin-treated dopaminergic neuronal cells because pretreatment with the PKCδ inhibitor rottlerin, or transfection and over-expression of catalytically inactive PKCδ(K)³⁷⁶(R), significantly attenuates dieldrin-induced DNA fragmentation and chromatin condensation. Together, we conclude that caspase-3-dependent proteolytic activation of PKCδ is a critical event in dieldrin-induced apoptotic cell death in dopaminergic neuronal cells.

  3. Involvement of COX2–thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Teraoka, Hiroki, E-mail: hteraoka@rakuno.ac.jp [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Peterson, Richard E. [School of Pharmacy, University of Wisconsin, Madison, WI (United States); Stegeman, John J. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States); Kitazawa, Takio; Hiraga, Takeo [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Kubota, Akira [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States)

    2014-09-15

    Highlights: • We establish a new indicator of pericardial edema in developing zebrafish (precardiac edema). • Property of precardiac edema by TCDD is similar to that for conventional pericardial edema. • COX2b (but not COX2a)–thromboxane pathway is involved in precardiac edema by TCDD. - Abstract: The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration–response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b

  4. The dioxin TCDD protects against aflatoxin-induced mutation in female rats, but not in male rats.

    Science.gov (United States)

    Thornton, A S; Oda, Y; Stuart, G R; Holcroft, J; de Boer, J G

    2004-07-11

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant and a potent carcinogen in laboratory rodents. When combined with other environmental toxins, it has been shown to increase the (geno)toxicity of some compounds. In this study, the effect of TCDD on the mutagenicity of aflatoxin-B1 (AFB1) was examined in the rat liver using a lacI transgenic rodent mutation assay. AFB1 induces GC-->TA transversions. Since TCDD is known to have a differential effect in male and female rodents, both sexes were studied. The data showed that a 6-week pre-exposure to TCDD had no significant effect on the frequency of aflatoxin-induced mutation in the liver of male rats. However, the TCDD treatment completely prevented the aflatoxin-induced transversion mutations in female animals.

  5. Gridded atmospheric emission inventory of 2,3,7,8-TCDD in China

    Science.gov (United States)

    Huang, Tao; Tian, Chongguo; Zhang, Kai; Gao, Hong; Li, Yi-Fan; Ma, Jianmin

    2015-05-01

    Establishment of the dioxins emission inventory has been considered as a crucial step toward risk assessment and elimination of dioxins contaminations. Based on a total dioxin emission inventory in China from different emission categories in 2004, this study created a gridded emission inventory of 2,3,7,8-TCDD, the most toxic congener in dioxins, in China in 2009 with a 1/4° longitude by 1/4° latitude resolution. It was estimated that annually total 371 ± 53 g (average ± standard deviation) of 2,3,7,8-TCDD was released into the atmosphere in 2009 over China, increasing approximately by 37% compared with its emission in 2004. Differing from most developed countries where municipal waste incinerations were regarded as a major atmospheric emission source, in China ferrous and non-ferrous metal production made the largest contribution to 2,3,7,8-TCDD air emission (138 ± 16 g), followed by waste incineration (109 ± 12 g), power and heating generation (62 ± 9 g), and production of mineral products (47 ± 8 g). The rest of sources contributed approximately 3% to the total 2,3,7,8-TCDD emission in 2009. Iron and steel industries are mainly located in Beijing-Tianjin-Hebei (BTH) and Yangtze River Delta (YRD) regions, whereas waste incinerators are mainly located in Pearl River Delta (PRD) region. Higher 2,3,7,8-TCDD emissions were found in these three regions. While the BTH, YRD, and PRD accounted for only about 4% of total land area of China, they contributed approximately 14%, 15%, and 5% to the total 2,3,7,8-TCDD emission in 2009 in China, respectively.

  6. Developmental toxicity of TCDD and related compounds: Species sensitivities and differences

    Energy Technology Data Exchange (ETDEWEB)

    Birnbaum, L.S.

    1991-01-01

    The issue of the developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds has been the subject of two recent reviews (Morrissey and Schwetz, 1989; Couture et al., 1990a). There is little doubt that TCDD is one of the most potent developmental toxins known, yet its production of frank structural malformations in species other than in the mouse are poorly described. The objective of the review is to critically address the role which TCDD and its approximate isostereomers have in causing a wide array of developmental effects in various species, including some very recent results. The bias of the author is that the teratogenic response of the mouse is a reflection of extreme sensitivity of the species to the induction of frank teratogenic responses in two epithelial tissues. That is, that the mouse is an outlier in the field of developmental toxicity, possibly in parallel to the exquisite sensitivity of the guinea pig vs the resistance of the hamster to the lethal effects of TCDD, or in the resistance of haired rodents to the induction of chloracne. The crucial point is that most species respond similarly to TCDD; for any given endpoint outliers will exist. However, no species is an outlier for all responses. In terms of developmental toxicity, essentially all species critically examined to date demonstrate potent developmentally toxic effects following exposure to TCDD and related chemicals. Relatively low doses to the dam (varying within an order of magnitude) result in embryo/fetal toxicity. The actual induction of terata is an extremely rare response. (Copyright (c) 1991 Cold Spring Harbor Laboratory Press.)

  7. Histological analysis of acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zodrow, Jeanmarie M.; Stegeman, John J.; Tanguay, Robert L

    2004-01-07

    Previous studies have demonstrated that acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by injection leads to inhibition of caudal fin regeneration in zebrafish. Since the TCDD exposure in these studies is systemic, it is possible that pathology in organs other than the fin could result in inhibition of fin regeneration. Therefore, histopathology of adult zebrafish (Danio rerio) organs was characterized following abdominal cavity injection of a TCDD dose (70 ng/g). The most pronounced histopathologic changes 5 days post-injection included lipidosis and hypertrophy of liver hepatocytes and hypertrophy of gill lamellae. Effects of TCDD exposure on immunolocalization of the zebrafish aryl hydrocarbon receptor nuclear translocator (ARNT2), the heterodimer partner of the aryl hydrocarbon receptor (AHR2), and an AHR regulated gene cytochrome P450 1A (CYP1A) was also determined. ARNT2 was immunolocalized to the gastrointestinal tract, gill lamellae, kidney, ventricle of the heart, caudal fin, brain and liver of zebrafish. TCDD exposure had no measurable effect on ARNT2 abundance or localization. CYP1A was immunolocalized in TCDD exposed fish as a biomarker for cells with an activated AHR pathway. CYP1A was not detected in any tissue from vehicle exposed fish. Significant TCDD-dependent induction of CYP1A was detected in the proximal tubules of the kidney, in liver hepatocytes and in the gastrointestinal tract of TCDD exposed fish. Significant but lower TCDD-dependent CYP1A expression was evident in the gill, caudal fin and ventricle of the heart. Overall, TCDD exposure in adult zebrafish leads to histopathology similar to that reported in other fish species, and it appears unlikely that the histopathology in these organs completely explains the inhibition of fin regeneration.

  8. Increased hepatic Igf2 gene expression involves C/EBPβ in TCDD-induced teratogenesis in rats.

    Science.gov (United States)

    Wang, Jun; Liu, Xiaoliang; Li, Tingting; Liu, Caixia; Zhao, Yanyan

    2011-11-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant for reproductive toxicity that was suggested to be linked to growth factors. Insulin-like growth factor 2 (Igf2) has great effects on the control of fetal growth. We hypothesize it might participate in the TCDD-induced toxic events. The expression of Igf2 in TCDD-induced fetal rat and rat hepatoma BRL-3A cells was monitored by real-time quantitative RT-PCR and Western blotting. Electrophoresis mobility shift assay and chromatin immunoprecipitation were performed to identify the CCAAT/enhancer binding protein β (C/EBPβ) responsive element in the Igf2 P3-promoter. The transcriptional activity of the Igf2 P3-promoter was detected by luciferase assay. Pregnant rats exposed to TCDD showed a modest incidence of fetal death, fetal growth restriction and fetal malformation. The levels of Igf2 mRNA and IGF2 protein were elevated in TCDD-exposed fetal liver. Temporal expression of Igf2 was also induced by TCDD in BRL-3A cells. A C/EBPβ responsive element was identified at position -743 to -732 of the Igf2 P3-promoter, and its binding was enhanced by TCDD exposure through upregulation of the C/EBPβ protein. The transcriptional activity of the Igf2 P3-promoter was also augmented by TCDD. Our results showed that TCDD may induce Igf2 gene expression through the transactivation of C/EBPβ, which may be linked to the developmental effects of TCDD in rats.

  9. TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin

    Energy Technology Data Exchange (ETDEWEB)

    De Abrew, K. Nadira [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Thomas-Virnig, Christina L.; Rasmussen, Cathy A. [Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States); Bolterstein, Elyse A. [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Schlosser, Sandy J. [Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States); Allen-Hoffmann, B. Lynn, E-mail: blallenh@wisc.edu [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States)

    2014-05-01

    The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial–stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin. - Highlights: • TCDD causes hyperkeratosis and basement membrane changes in a model of human skin. • TCDD induces MMP-10 expression in organotypic cultures

  10. Comparative metagenomic analysis of soil microbial communities across three hexachlorocyclohexane contamination levels.

    Directory of Open Access Journals (Sweden)

    Naseer Sangwan

    Full Text Available This paper presents the characterization of the microbial community responsible for the in-situ bioremediation of hexachlorocyclohexane (HCH. Microbial community structure and function was analyzed using 16S rRNA amplicon and shotgun metagenomic sequencing methods for three sets of soil samples. The three samples were collected from a HCH-dumpsite (450 mg HCH/g soil and comprised of a HCH/soil ratio of 0.45, 0.0007, and 0.00003, respectively. Certain bacterial; (Chromohalobacter, Marinimicrobium, Idiomarina, Salinosphaera, Halomonas, Sphingopyxis, Novosphingobium, Sphingomonas and Pseudomonas, archaeal; (Halobacterium, Haloarcula and Halorhabdus and fungal (Fusarium genera were found to be more abundant in the soil sample from the HCH-dumpsite. Consistent with the phylogenetic shift, the dumpsite also exhibited a relatively higher abundance of genes coding for chemotaxis/motility, chloroaromatic and HCH degradation (lin genes. Reassembly of a draft pangenome of Chromohalobacter salaxigenes sp. (∼8X coverage and 3 plasmids (pISP3, pISP4 and pLB1; 13X coverage containing lin genes/clusters also provides an evidence for the horizontal transfer of HCH catabolism genes.

  11. Age-related changes in rat testicular oxidative stress parameters by hexachlorocyclohexane

    Energy Technology Data Exchange (ETDEWEB)

    Samanta, L.; Sahoo, A.; Chainy, G.B.N. [Biochemistry Unit, Department of Zoology, Utkal University, Bhubaneswar (India)

    1999-03-01

    Effect of repeated oral administration of hexachlorocyclohexane (HCH; 10 and 20 mg/kg body weight per day for 7, 15 and 30 days) on antioxidant defence system and lipid peroxidation (LPX) in the testis was compared between immature (15-day-old) and mature (90-day-old) rats. In both age-groups of rats, the pesticide elicited a significant decrease in the activities of cytosolic superoxide dismutase (SOD; total and CN{sup -}-resistant) and catalase, and ascorbic acid content together with an increase in the levels of LPX (both in crude homogenate and subcellular fractions) and H{sub 2}O{sub 2}. Testicular glutathione peroxidase (GPx; total and non-selenium-dependent) activity was enhanced in both the age-groups of rats while the testicular glutathione content as well as glutathione reductase activity remained unaltered. HCH treatment resulted in a decrease of total epididymal sperm number with a higher incidence of dead and damaged spermatozoa, and sperms having anomalous head. Statistical analyses suggest that the alterations in the testicular antioxidant defence profile in the rat are not only dependent on the duration of pesticide treatment, but also influenced by age. (orig.) With 6 figs., 3 tabs., 45 refs.

  12. Phytotoxicity of hexachlorocyclohexane: Effect on germination and early growth of different plant species.

    Science.gov (United States)

    Calvelo Pereira, R; Monterroso, C; Macías, F

    2010-04-01

    The aim of the present study was to select candidate plant species for phytoremediation of soils contaminated with hexachlorocyclohexane (HCH). For this purpose, an experiment was carried out under controlled conditions of germination and growth, with nine plant species of economic and/or agricultural interest, in a soil contaminated with a heterogeneous mixture (at eight different levels of contamination) of the main HCH isomers (alpha-, beta-, gamma- and delta-HCH). The results revealed differences in the plant responses to the control soil and the soils containing HCH. Germination was not as strongly affected as other parameters such as the rate of germination and seedling vigour. In general, all of the species displayed signs of stress in response to the presence of HCH, although to different degrees. Some of the species used in the experiment (Hordeum vulgare L., Brassica sp., Phaseoulus vulgaris L.) were capable of mitigating the negative effects of HCH, and displayed a certain degree of resistance, as their biomass production was not greatly affected by the contaminant. These (tolerant) plants therefore appear to be ideal for phytoremediation purposes.

  13. Dynamic fate modeling of γ-hexachlorocyclohexane in the lower reaches of the Liao River

    Institute of Scientific and Technical Information of China (English)

    LIU Zhenyu; YANG Fenglin; QUAN Xie; ZHANG Xiaohong

    2007-01-01

    A QWASI model dependent on temperature is parameterized to describe the long-term fate of persistent organic pollutants(POPs)in the Liao River.The model parameters,namely fugacity capacity,degradation rate,and transfer coefficient,are profoundly affected by temperature.This model is used to simulate the fate Of γ-hexachlorocyclohexane(γ-HCH)in the lower reaches of the Liao River from 1998 to 2008.Modeling results show that γ-HCH fugacity capacities in air,water,and sediment increase as temperature decreases.and the transfer and transformation rate coefficients increase as temperature increases.The variations of transfer and transformation parameter D values depend on fugacity capacities,and transfer and transformation coefficients simultaneously.The performance of the model is evaluated by comparing the predicted and observed concentrations in the water and sediment of the Liao River.The predicted values agree well with the observed value in the order of magnitude,in most cases within the factor of 3.It iS believed that the model is appropriate for simulating the long term fate of POPs in the Liao River.

  14. Engineering bacteria for bioremediation of persistent organochlorine pesticide lindane (γ-hexachlorocyclohexane).

    Science.gov (United States)

    Chaurasia, Akhilesh Kumar; Adhya, Tapan Kumar; Apte, Shree Kumar

    2013-12-01

    Strategies were designed for bioremediation of the highly persistent toxic pesticide γ-hexachlorocyclohexane (γ-HCH) or lindane from the environment. Lindane caused the loss of stress-protective chaperone GroEL, and inhibited photosynthesis, respiration and nitrogen-fixation in Anabaena, resulting in growth arrest. To alleviate lindane toxicity, the linA2 gene, encoding HCH dehydrochlorinase from Sphingomonas paucimobilis B90, was knocked-in at an innocuous locus in Anabaena genome and over-expressed from an eco-friendly light-inducible PpsbA1 promoter. The recombinant Anabaena degraded >98% of 10 ppm lindane within 6-10 days. A LinA2 overexpressing Escherichia coli strain could degrade 10 ppm of all the isomers of lindane within 1h and displayed a visual degradation zone on a newly designed histochemical plate containing 50mg lindane within 12h. The study demonstrates (a) bioremediation of traces of lindane prevalent in paddy fields, using bioengineered photoautotrophic Anabaena, and, (b) biodegradation of huge stockpiles of lindane, by employing recombinant live/dead E. coli.

  15. Devosia lucknowensis sp. nov., a bacterium isolated from hexachlorocyclohexane (HCH) contaminated pond soil.

    Science.gov (United States)

    Dua, Ankita; Malhotra, Jaya; Saxena, Anjali; Khan, Fazlurrahman; Lal, Rup

    2013-10-01

    Strain L15(T), a Gram-negative, motile, orange colored bacterium was isolated from pond soil in the surrounding area of a hexachlorocyclohexane (HCH) dump site at Ummari village in Lucknow, India. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain L15(T) belongs to the family Hyphomicrobiaceae in the order Rhizobiales. Strain L15(T) showed highest 16S rRNA gene sequence similarity to Devosia chinhatensis IPL18(T) (98.0%). Chemotaxonomic data revealed that the major fatty acids were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C18:1 ω7c 11-methyl, C16:0 and C18:0. The major polar lipids of strain L15(T) were diphosphatidylglycerol and phosphatidylglycerol. The genomic DNA G+C content of strain L15(T) was 59.8%. Polyamine profile showed the presence of sym-homospermidine with traces of putrescine. Ubiquinone Q-10 was the major respiratory quinone present. Based on these data, strain L15(T) (=CCM 7977(T) =DSM 25398(T)) was classified as a type strain of a novel species, for which the name Devosia lucknowensis sp. nov. is proposed.

  16. Effects of electron donors on the microbial reductive dechlorination of hexachlorocyclohexane and on the environment.

    Science.gov (United States)

    Cui, Zhaojie; Meng, Fanli; Hong, Jinglan; Li, Xiangzhi; Ren, Xiaohua

    2012-06-01

    The reductive biotransformation of α-, β-, γ-, and δ-hexachlorocyclohexane isomers was investigated using five alternative electron donors (i.e., glucose plus methanol, glucose only, methanol only, acetate, and ethanol) in a batch assay of an HCH-dechlorinating anaerobic culture. In addition, a life cycle assessment was conducted using the IMPACT2002+ method to evaluate the environmental effects of HCH bioremediation with the aforementioned electron donors. Results showed that the electron donors methanol plus glucose, ethanol, glucose, and methanol can significantly enhance the biotransformation of each HCH isomer. However, the amended electron donors and the byproduct of the anoxic/anaerobic systems may negatively affect the environment (e.g., respiratory inorganic, land occupation, global warming, and non-renewable energy categories). These effects are attributed to the electron donor production processes. To avoid secondary pollutants, a linear relationship between the upper bound electron donor applications and HCH concentration was observed from an environmental perspective. Results indicated that the methanol scenario was the most suitable option for the current research.

  17. Laboratory and field scale bioremediation of hexachlorocyclohexane (HCH) contaminated soils by means of bioaugmentation and biostimulation.

    Science.gov (United States)

    Garg, Nidhi; Lata, Pushp; Jit, Simran; Sangwan, Naseer; Singh, Amit Kumar; Dwivedi, Vatsala; Niharika, Neha; Kaur, Jasvinder; Saxena, Anjali; Dua, Ankita; Nayyar, Namita; Kohli, Puneet; Geueke, Birgit; Kunz, Petra; Rentsch, Daniel; Holliger, Christof; Kohler, Hans-Peter E; Lal, Rup

    2016-06-01

    Hexachlorocyclohexane (HCH) contaminated soils were treated for a period of up to 64 days in situ (HCH dumpsite, Lucknow) and ex situ (University of Delhi) in line with three bioremediation approaches. The first approach, biostimulation, involved addition of ammonium phosphate and molasses, while the second approach, bioaugmentation, involved addition of a microbial consortium consisting of a group of HCH-degrading sphingomonads that were isolated from HCH contaminated sites. The third approach involved a combination of biostimulation and bioaugmentation. The efficiency of the consortium was investigated in laboratory scale experiments, in a pot scale study, and in a full-scale field trial. It turned out that the approach of combining biostimulation and bioaugmentation was most effective in achieving reduction in the levels of α- and β-HCH and that the application of a bacterial consortium as compared to the action of a single HCH-degrading bacterial strain was more successful. Although further degradation of β- and δ-tetrachlorocyclohexane-1,4-diol, the terminal metabolites of β- and δ-HCH, respectively, did not occur by the strains comprising the consortium, these metabolites turned out to be less toxic than the parental HCH isomers.

  18. Identification of aryl hydrocarbon receptor signaling pathways altered in TCDD-treated red seabream embryos by transcriptome analysis.

    Science.gov (United States)

    Iida, Midori; Fujii, Satoshi; Uchida, Masaya; Nakamura, Hiroshi; Kagami, Yoshihiro; Agusa, Tetsuro; Hirano, Masashi; Bak, Su-Min; Kim, Eun-Young; Iwata, Hisato

    2016-08-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces a broad spectrum of toxic effects including craniofacial malformation and neural damage in fish embryos. These effects are mainly mediated by the aryl hydrocarbon receptor (AHR). However, the mode of action between TCDD-induced AHR activation and adverse outcomes is not yet understood. To provide a comprehensive picture of the AHR signaling pathway in fish embryos exposed to TCDD, red seabream (Pagrus major) embryos were treated with graded concentrations of TCDD (0.3-37nM) in seawater, or with a mixture of TCDD and 500nM CH223191, an AHR-specific antagonist. The transcriptome of red seabream embryos was analyzed using a custom-made microarray with 6000 probes specifically prepared for this species. A Jonckheere-Terpstra test was performed to screen for genes that demonstrated altered mRNA expression levels following TCDD exposure. The signals of 1217 genes (as human homologs) were significantly altered in a TCDD concentration-dependent manner (q-valueTCDD-induced alteration in mRNA expression was alleviated by co-exposure to CH223191, suggesting that the mRNA expression level of these genes was regulated by AHR. To identify TCDD-activated pathways, the microarray data were further subjected to gene set enrichment analysis (GSEA) and functional protein-protein interaction (PPI) network analysis. GSEA demonstrated that the effects of TCDD on sets of genes involved calcium, mitogen-activated protein kinase (MAPK), actin cytoskeleton, chemokine, T cell receptor, melanoma, vascular endothelial growth factor (VEGF), axon guidance, and renal cell carcinoma signaling pathways. These results suggest the hypotheses that TCDD induces immunosuppression via the calcium, MAPK, chemokine, and T cell receptor signaling pathways, neurotoxicity via VEGF signaling, and axon guidance alterations and teratogenicity via the dysregulation of the actin cytoskeleton and melanoma and renal cell carcinoma signaling pathways. Furthermore

  19. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells

    OpenAIRE

    2015-01-01

    The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to i...

  20. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease.

    Science.gov (United States)

    Richardson, Jason R; Caudle, W Michael; Wang, Minzheng; Dean, E Danielle; Pennell, Kurt D; Miller, Gary W

    2006-08-01

    Exposure to pesticides has been suggested to increase the risk of Parkinson's disease (PD), but the mechanisms responsible for this association are not clear. Here, we report that perinatal exposure of mice during gestation and lactation to low levels of dieldrin (0.3, 1, or 3 mg/kg every 3 days) alters dopaminergic neurochemistry in their offspring and exacerbates MPTP toxicity. At 12 wk of age, protein and mRNA levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were increased by perinatal dieldrin exposure in a dose-related manner. We then administered MPTP (2 x 10 mg/kg s.c) at 12 wk of age and observed a greater reduction of striatal dopamine in dieldrin-exposed offspring, which was associated with a greater DAT:VMAT2 ratio. Additionally, dieldrin exposure during development potentiated the increase in GFAP and alpha-synuclein levels induced by MPTP, indicating increased neurotoxicity. In all cases there were greater effects observed in the male offspring than the female, similar to that observed in human cases of PD. These data suggest that developmental exposure to dieldrin leads to persistent alterations of the developing dopaminergic system and that these alterations induce a "silent" state of dopamine dysfunction, thereby rendering dopamine neurons more vulnerable later in life.

  1. In Utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood.

    Science.gov (United States)

    Ricke, William A; Lee, Calvin W; Clapper, Tyler R; Schneider, Andrew J; Moore, Robert W; Keil, Kimberly P; Abler, Lisa L; Wynder, Jalissa L; López Alvarado, Arnaldo; Beaubrun, Isaac; Vo, Jenny; Bauman, Tyler M; Ricke, Emily A; Peterson, Richard E; Vezina, Chad M

    2016-04-01

    Benign prostatic hyperplasia, prostate cancer, and changes in the ratio of circulating testosterone and estradiol often occur concurrently in aging men and can lead to lower urinary tract (LUT) dysfunction. To explore the possibility of a fetal basis for the development of LUT dysfunction in adulthood, Tg(CMV-cre);Nkx3-1(+/-);Pten(fl/+) mice, which are genetically predisposed to prostate neoplasia, were exposedin uteroand during lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 μg/kg po) or corn oil vehicle (5 ml/kg) after a single maternal dose on 13 days post coitus, and subsequently were aged without further manipulation, or at 8 weeks of age were exposed to exogenous 17 β-estradiol (2.5 mg) and testosterone (25 mg) (T+E2) via slow release subcutaneous implants.In uteroand lactational (IUL) TCDD exposure in the absence of exogenous hormone treatment reduced voiding pressure in adult mice, but otherwise had little effect on mouse LUT anatomy or function. By comparison, IUL TCDD exposure followed by exogenous hormone treatment increased relative kidney, bladder, dorsolateral prostate, and seminal vesicle weights, hydronephrosis incidence, and prostate epithelial cell proliferation, thickened prostate periductal smooth muscle, and altered prostate and bladder collagen fiber distribution. We propose a 2-hit model whereby IUL TCDD exposure sensitizes mice to exogenous-hormone-induced urinary tract dysfunction later in life.

  2. TCDD AND EGF AFFECT MAPK PATHWAY ACTIVATION IN MURINE EMBRYONIC PALATE

    Science.gov (United States)

    Palatal fusion occurs on GD 14-15 in the mouse, accompanied by a decrease in EGF receptor (EGFR) at the medial edge of the palatal shelves. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces cleft palate and maintains EGF and EGF receptor (EGFR) expression levels in the medial ed...

  3. Total PCBs, TCDD-EQs in eggs: Reproductive hazards to north Pacific albatrosses

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, J.P.; Auman, H.J.; Summer, C.L.; Giesy, J.P.; Sanderson, J.T.; DeDoes, J.M.; Verbrugge, D.A.; Jones, P.

    1995-12-31

    Freshly laid eggs of Laysan and black-footed Albatrosses (Diomedea immutabilis and D. nigripes) were collected at Midway Atoll 1992 through 1994 and subsequently analyzed for chlorinated contaminants including OC pesticides, PCBs, dioxins and furans. TCDD-EQs in eggs were calculated from congener-specific data. Total PCBs ranged from 1.1 to 3.8 mglkg ww. Calculated TCDD-EQs ranged from 52--124 pg/g. A substantial portion (30--35%) of the TCDD-EQs in eggs were owing to dioxins and furans, and the balance to PCBs. PCBs in albatross eggs were much less potent than PCBs from waterbirds` eggs of the Great Lakes and other continental inland waters. Hazard indices based on calculated TCDD-EQs suggested that Laysan eggs were at the LOAEL for embryonic effects, but black-footed eggs were well above avian LOAELS. Egg death during natural incubation was 2--3% greater in black-footed than Laysan nests, and 5% fewer black-footed albatross chicks were fledged in 1994. A low incidence of deformities in hatchlings was noted in 1994 and 1995. Crossed-bill hatchlings were not reported in these populations until the late 1970s in spite of intensive studies 1957--1972, but occurred at rates of 1 in 14,000 hatchlings, and 1 in 300 dead eggs 1993--1995. Reproductive effects owing to contaminant exposures in these most pelagic seabirds are confirmed.

  4. Agent Orange Exposure and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in Human Milk.

    Science.gov (United States)

    Scialli, Anthony R; Watkins, Deborah K; Ginevan, Michael E

    2015-06-01

    Agent Orange was sprayed in parts of southern Vietnam during the U.S.-Vietnam war and was a mixture of two chlorophenoxy herbicides. The mixture was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other dioxins and furans are measurable in the milk of Vietnamese women. We explored whether the TCDD in milk from these women was from Agent Orange and whether lactational exposure can be a mode of transgenerational effects of TCDD from Agent Orange. A review of the world's literature on milk concentrations of polychlorinated compounds showed the presence of TCDD and other dioxins and furans in all countries that have been assessed. The congener profile of these chemicals, that is, the proportion of different congeners in the sample, can be used to assess the source of milk contamination. Measurements in most countries, including contemporary measurements in Vietnam, are consistent with non-Agent Orange exposure sources, including industrial activities and incineration of waste. Models and supporting human data suggest that TCDD from breastfeeding does not persist in a child past adolescence and that the adult body burden of TCDD is independent of whether the individual was breast- or bottle-fed as a child. These findings suggest that exposure to Agent Orange in Vietnam did not result in persistent transgenerational exposure through human milk.

  5. Toxicogenomic evaluation of long-term hepatic effects of TCDD in immature, ovariectomized C57BL/6 mice.

    Science.gov (United States)

    Kopec, Anna K; Boverhof, Darrell R; Nault, Rance; Harkema, Jack R; Tashiro, Colleen; Potter, Dave; Sharratt, Bonnie; Chittim, Brock; Zacharewski, Timothy R

    2013-10-01

    Acute exposure to hepatotoxic doses of 2,3,7,8-tetrachloro- dibenzo-p-dioxin (TCDD) in mice is characterized by differential gene expression that can be phenotypically anchored to elevated levels of serum alanine aminotransferase, increased relative liver weights, hepatic steatosis, inflammation, and hepatocellular necrosis. Unlike most studies that focus on acute exposure effects, this study evaluated the long-term effects of a single oral gavage of 30 μg/kg TCDD at 1, 4, 12, 24, 36, and 72 weeks postdose in ovariectomized C57BL/6 mice. Hepatic TCDD levels were almost completely eliminated by 24 weeks with a calculated half-life of 12 days. Hepatic gene expression analysis identified 395 unique differentially expressed genes between 1 and 12 weeks that decreased to ≤ 8 by 72 weeks, consistent with the minimal hepatic TCDD levels. Hepatic vacuolization, characteristic of short-term exposure, subsided by 4 weeks. Similarly, TCDD-elicited hepatic necrosis and inflammation dissipated by 1 week. Collectively, these results suggest that TCDD-elicited histologic and gene expression responses can be correlated to elevated hepatic TCDD levels, which, once eliminated, elicit minimal hepatic gene expression and histologic alterations.

  6. The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice

    Energy Technology Data Exchange (ETDEWEB)

    Connor, M.J. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Puhvel, S.M. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Sakamoto, M. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Nanthur, J. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States))

    1994-12-01

    In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 [mu]g TCDD/kg body weight on postnatal day 0. At 12 [mu]g/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 [mu]g/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice. (orig.)

  7. Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD

    Energy Technology Data Exchange (ETDEWEB)

    Prokopec, Stephenie D.; Watson, John D. [Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Lee, Jamie [Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Pohjanvirta, Raimo [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio Finland (Finland); Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki (Finland); Boutros, Paul C., E-mail: Paul.Boutros@oicr.on.ca [Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2015-04-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500 μg/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. - Highlights: • Differences exist between the toxicity phenotypes to TCDD in male and female mice. • TCDD-mediated transcriptomic differences were identified between the sexes. • Resistant female mice displayed a large, early-onset, transcriptomic response.

  8. DIELDRIN INDUCES CYTOSOLIC 7,12-[3H-]DIMETHYLBENZ[A]ANTHRACENE BINDING BUT NOT MULTIDRUG RESISTANCE PROTEINS IN RAINBOW TROUT LIVER.

    Science.gov (United States)

    Previously it was demonstrated that biliary excretion of a single dose of [14C]dieldrin or [3H]7,12-dimethylbenz[a]anthracene (DMBA) was stimulated up to 700% and 300%, respectively, in rainbow trout fed 0.3-0.4 mg dieldrin/kg/d for 9-12 wk. This was not explained by increased ac...

  9. DIELDRIN INDUCES CYTOSOLIC 7,12-[3H-]DIMETHYLBENZ[A]ANTHRACENE BINDING BUT NOT MULTIDRUG RESISTANCE PROTEINS IN RAINBOW TROUT LIVER.

    Science.gov (United States)

    Previously it was demonstrated that biliary excretion of a single dose of [14C]dieldrin or [3H]7,12-dimethylbenz[a]anthracene (DMBA) was stimulated up to 700% and 300%, respectively, in rainbow trout fed 0.3-0.4 mg dieldrin/kg/d for 9-12 wk. This was not explained by increased ac...

  10. Dieldrin promotes proteolytic cleavage of poly(ADP-ribose) polymerase and apoptosis in dopaminergic cells: protective effect of mitochondrial anti-apoptotic protein Bcl-2.

    Science.gov (United States)

    Kitazawa, Masashi; Anantharam, Vellareddy; Kanthasamy, Arthi; Kanthasamy, Anumantha G

    2004-06-01

    Previously, we demonstrated that the organochlorine pesticide dieldrin induces mitochondrial depolarization, caspase-3 activation and apoptosis in dopaminergic PC12 cells. We also demonstrated that protein kinase Cdelta (PKCdelta), a member of a novel PKC family of proteins, is proteolytically activated by caspase-3 to mediate apoptotic cell death processes. In the present study, we have further characterized the protective effect of the major mitochondrial anti-apoptotic protein Bcl-2 against dieldrin-induced apoptotic events in dopaminergic cells. Exposure to dieldrin (30-100 microM) produced significant cytotoxicity and caspase-3 activation within 3h in vector-transfected PC12 cells, whereas human Bcl-2-transfected PC12 cells were almost completely resistant to dieldrin-induced cytotoxicity and caspase-3 activation. Also, dieldrin (30-300 microM) treatment induced proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), which was blocked by pretreatment with caspase-3 inhibitors Z-DEVD-FMK and Z-VAD-FMK. Additionally, dieldrin-induced chromatin condensation and DNA fragmentation were completely blocked in Bcl-2-overexpressed PC12 cells as compared to vector control cells. Together, these results clearly indicate that overexpression of mitochondrial anti-apoptotic protein protects against dieldrin-induced apoptotic cell death and further suggest that dieldrin primarily alters mitochondrial function to initiate apoptotic cell death in dopaminergic cells.

  11. TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    Directory of Open Access Journals (Sweden)

    Tien-Ling Liao

    2014-09-01

    Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  12. ARTICLES: Theoretical Study on Destruction Mechanism of 2,3,7,8-TCDD by O3 and NO3

    Science.gov (United States)

    Wang, Zhi-hua; Wen, Zheng-cheng; Xu, Jiang-rong; Zhou, Jun-hu; Cen, Ke-fa

    2010-06-01

    In order to improve the destruction efficiency of dioxins and also for developing new dioxin control technology, the destruction mechanisms of 2,3,7,8-tetrachlorodihenzo-p-dioxin (2,3,7,8-TCDD) by O3 and NO3, were investigated employing quantum chemical calculations. For involved reactions, the microcosmic reaction processes were analyzed and depicted in detail based on geometry optimizations made by the B3LYP/6-31G(d) method. At the same time, the reaction activation energies were also calculated at the MP2/6-311G(d,p)//B3LYP/6-31G(d) level. Configuration analysis indicated that 2,3,7,8-TCDD could be destroyed by O3 and NO3 in two different ways. The destruction of 2,3,7,8-TCDD by O3 proceeded via the addition of O3 and the cleavage of C = C while the destruction of 2,3,7,8-TCDD by NO3 proceeded via the substitution of chlorine by NO3. Calculated results show that, the activation energy of the destruction reaction of 2,3,7,8-TCDD by NO3 (267.48 kJ/mol) is much larger than that of the destruction reaction of 2,3,7,8-TCDD by O3 (51.20 kJ/mol). This indicated that the destruction of 2,3,7,8-TCDD by O3 is much more efficient than that of 2,3,7,8-TCDD by NO3. The reason why the activation energy for the destruction reaction of 2,3,7,8-TCDD by NO3 is so large, is also discussed.

  13. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

    Science.gov (United States)

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G

    1993-12-01

    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Effect of Plant Growth Regulators on Phytoremediation of Hexachlorocyclohexane-Contaminated Soil.

    Science.gov (United States)

    Chouychai, Waraporn; Kruatrachue, Maleeya; Lee, Hung

    2015-01-01

    The influence of three plant growth regulators, indolebutyric acid (IBA), thidiazuron (TDZ) and gibberellic acid (GA3), either individually or in pair-wise combinations, on the ability of waxy corn plant to remove hexachlorocyclohexane (HCH) from contaminated soil was studied. Waxy corn seeds were immersed for 3 h in solutions of 1.0 mg/l IBA, 0.01 mg/l TDZ, 0.1 mg/l GA3, or a mixture of two of the growth regulators, and then inoculated in soil contaminated with 46.8 mg/kg HCH for 30 days. Pretreatment of corn seeds with the plant growth regulators did not enhance corn growth when compared with those immersed in distilled water (control), but the pretreatment enhanced HCH removal significantly. On day 30, HCH concentration in the bulk soil planted with corn seeds pretreated with GA3 or TDZ+GA3 decreased by 97.4% and 98.4%, respectively. In comparison, HCH removal in soil planted with non-pretreated control waxy corn seeds was only 35.7%. The effect of several growth regulator application methods was tested with 0.01 mg/l TDZ. The results showed that none of the methods, which ranged from seed immersion, watering in soil, or spraying on shoots, affected HCH removal from soil. However, the method of applying the growth regulators may affect corn growth. Watering the corn plant with TDZ in soil led to higher root fresh weight (2.2 g) and higher root dried weight (0.57 g) than the other treatments (0.2-1.7 g root fresh weight and 0.02-0.43 g root dried weight) on day 30. Varying the concentrations of GA3 did not affect the enhancement of corn growth and HCH removal on day 30. The results showed that plant growth regulators may have potential for use to enhance HCH phytoremediation.

  15. Sphingomonas laterariae sp. nov., isolated from a hexachlorocyclohexane-contaminated dump site.

    Science.gov (United States)

    Kaur, Jasvinder; Kaur, Jaspreet; Niharika, Neha; Lal, Rup

    2012-12-01

    A Gram-staining-negative, non-motile, cream-coloured and rod-shaped bacterium, designated strain LNB2(T), was isolated from a hexachlorocyclohexane-contaminated dump site in the village of Ummari, in northern India. The taxonomic position of the novel strain was investigated by using a polyphasic approach. In a phylogenetic analysis based on 16S rRNA gene sequences, strain LNB2(T) appeared to be most closely related to Sphingomonas haloaromaticamans A175(T) (98.0% sequence similarity) and Sphingomonas histidinilytica UM2(T) (97.3%). In DNA-DNA hybridizations, the levels of DNA-DNA relatedness between the novel strain and S. haloaromaticamans A175(T) and S. histidinilytica UM2(T) were found to be low (8.6% and 5.6%, respectively). The genomic DNA G+C content of strain LNB2(T) was 61.0 mol%. The novel strain's predominant fatty acids were summed feature 8 (C(18:1)ω7c and/or C(18:1)ω6c), C(16:0), summed feature 3 (C(16:1)ω7c and/or C(16:1)ω6c), C(14:0) 2-OH, C(17:1)ω6c and 11-methyl C(18:1)ω7c. The major ubiquinone was Q-10, the predominant polyamine was homospermidine, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, sphingoglycolipid, phosphatidylethanolamine and phosphatidyldimethylethanolamine. Based on the phylogenetic, biochemical and chemotaxonomic evidence and the results of the DNA-DNA hybridizations, strain LNB2(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas laterariae sp. nov. is proposed. The type strain is LNB2(T) ( = MTCC 10873(T) = CCM 7880(T) = DSM 25432(T)).

  16. Distribution of dichlorodiphenyltrichloroethane and hexachlorocyclohexane in urban soils and risk assessment

    Directory of Open Access Journals (Sweden)

    Bhupander Kumar

    2012-12-01

    Full Text Available This study deals with the distribution of dichlorodiphenyltrichloroethanes (DDTs and hexachlorocyclohexanes (HCHs in urban soils, their possible sources and probabilistic human and environmental health risk. The average concentrations of total HCHs and total DDTs in the soils were in the range of 0.56-8.52 mg kg–1 and 0.54-37.42 mg kg–1, respectively, which were lower than guideline limits. The compositional analysis of HCH isomers reflects contaminations from recent usage. However, isomeric ratios between DDT, DDE and DDD, indicate anaerobic degradation of DDT and contaminations from aged DDT. Human and environmental health risk assessment was carried out by the estimation of lifetime average daily dose (LADD, incremental life time cancer risk (ILCR and non carcinogenic health hazard quotient (HQ. LADD of total pesticides (HCH and DDT for human adults and children was ranged between 3.3x10–9-6.6x10–8 mg kg–1d–1 and 1.7x10–8-3.4x10–7 mg kg–1 d–1, respectively. The cumulative ILCR for adults and children was ranged from 5.1x10–9 to 4.6x10–8 and 2.6x10–8 to 2.4x10–7, respectively. The HQ was ranged between 1.8x10–6- 1.4x10–4 and 9.5x10–6-7.2x10–4, respectively for adults and children. These estimated ILCR and HQ were within the safe acceptable limits, indicating negligible risk to the residents of the study area.

  17. Modeling of gene expression pattern alteration by p,p′-DDE and dieldrin in largemouth bass

    Science.gov (United States)

    Garcia-Reyero, Natalia; Barber, David; Gross, Timothy; Denslow, Nancy

    2006-01-01

    In this study, largemouth bass (LMB) were subchronically exposed to p,p′-DDE or dieldrin in their diet to evaluate the effect of exposure on expression of genes involved in reproduction and steroid homeostasis. Using real-time PCR, we detected a different gene expression pattern for each OCP, suggesting that they each affect LMB in a different way. We also detected a different expression pattern among sexes, suggesting that sexes are affected differently by OCPs perhaps reflecting the different adaptive responses of each sex to dysregulation caused by OCP exposure.

  18. Modeling of gene expression pattern alteration by p,p'-DDE and dieldrin in largemouth bass.

    Science.gov (United States)

    Garcia-Reyero, Natàlia; Barber, David; Gross, Timothy; Denslow, Nancy

    2006-07-01

    In this study, largemouth bass (LMB) were subchronically exposed to p,p'-DDE or dieldrin in their diet to evaluate the effect of exposure on expression of genes involved in reproduction and steroid homeostasis. Using real-time PCR, we detected a different gene expression pattern for each OCP, suggesting that they each affect LMB in a different way. We also detected a different expression pattern among sexes, suggesting that sexes are affected differently by OCPs perhaps reflecting the different adaptive responses of each sex to dysregulation caused by OCP exposure.

  19. Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD.

    Science.gov (United States)

    Prokopec, Stephenie D; Watson, John D; Lee, Jamie; Pohjanvirta, Raimo; Boutros, Paul C

    2015-04-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500μg/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear.

  20. Removal of endrin and dieldrin isomeric pesticides through stereoselective adsorption behavior on the graphene oxide-magnetic nanoparticles.

    Science.gov (United States)

    Shrivas, Kamlesh; Ghosale, Archana; Nirmalkar, Nidhi; Srivastava, Arti; Singh, Sunil Kumar; Shinde, Sandip S

    2017-09-16

    A novel stereoselective removal behavior of isomeric endrin and dieldrin pesticides from sample solution is demonstrated using nanocomposite of graphene oxide (GO) and iron oxide (Fe3O4) magnetic nanoparticles (MNPs). The removal efficiency of endrin and dieldrin was found higher when GO-MNPs was used as a separating probe than the individual use of GO and MNPs. The removal efficiency of both the pesticides was found to be more favorable when the dosage amount of GO-MNPs was 30 mg for 30-min contact time with pH 4.0 at room temperature. The good correlation of determination (R (2)) with 0.975 and 0.973 values obtained for endrin and dieldrin, respectively demonstrated a well fitting of Langmuir adsorption isotherm model. The higher removal percentage (86.0%) and higher slope value of Langmuir adsorption isotherm were estimated for endrin compared to dieldrin (74.0%). The reason for higher adsorption percentage of endrin is due to the endo-position of oxygen atom in molecule favors more interaction of molecules with GO-MNPs compared to the exo-position of oxygen present in dieldrin. In addition, the higher value of R (2) for endrin and dieldrin demonstrated better suitability of pseudo-first-order and pseudo-second-order kinetic models, respectively. The advantages of the present method are use of simple UV-vis spectrophotometry for monitoring and low-cost use of GO-MNPs nanomaterial for the removal of pesticides from sample solution.

  1. The sublethal effects of the organochlorines dieldrin and lindane on growth and reproduction of Eudrilus eugeniae and Eisenia fetida (Oligochaeta

    Directory of Open Access Journals (Sweden)

    Editorial Office

    1994-07-01

    Full Text Available Experimental exposure of the earthworm species Eudrilus eugeniae to organochlorines showed that dieldrin causes damage to sperm ultrastructure when viewed electronmicroscopically. Worms containing concentrations of 7,27 mg/kg dieldrin and higher showed more than 10% sperm damage. Exposure of Eisenia fetida to sublethal concentrations of lindane did not result in sperm damage but demonstrated an increase in growth and reproductive activity. It is argued that quantification of sperm damage and correlation with pesticide concentration could provide a useful tool for evaluating environmental quality. Furthermore, the effects of sublethal concentrations of pesticides that manifest themselves in increased growth and reproductive activity could affect ecological balances.

  2. Dieldrin stimulates biliary excretion of 14C-benzo[a]pyrene polar metabolites but does not change the biliary metabolite profile in rainbow trout (Oncorhyncus mykiss).

    Science.gov (United States)

    Barnhill, Melanie L; Rosemond, Marie V M; Curtis, Lawrence R

    2003-10-01

    Activities of hepatic microsomal and cytosolic epoxide hydrolases, accumulation of dieldrin in liver, and in vivo metabolism and disposition of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP), were examined in rainbow trout pretreated with dieldrin, a chlorinated cyclodiene insecticide. Rainbow trout were fed 0.3 mg dieldrin/kg/day for 9 weeks and the same dose of dieldrin for 9 weeks, followed by 3 weeks on control diet (12 weeks). Fish then received an intraperitoneal (ip) challenge dose of 14C-BP (10 micromol/kg). Dieldrin pretreatment significantly elevated the concentration of 14C-BP in bile (142% and 200% at 9 and 12 weeks, respectively), but not liver or fat. Extraction of bile subsamples confirmed dieldrin pretreatment significantly stimulated total biliary excretion of 14C-BP polar metabolites (244% and 221% at week 9 and 12, respectively). The complex metabolism of BP characterized the in vivo state of the CYP system, UDP-glucuronyltransferases, and sulfotransferases. Bile was extracted and then hydrolyzed by beta-glucuronidase and arylsulfatase to regenerate BP metabolites conjugated by phase II enzymes. Evaluation of biliary polar metabolite profiles of 14C-BP revealed no significant differences between control and dieldrin-fed fish. There was no selective enhancement of any particular metabolite, or formation of a novel metabolite with dieldrin pretreatment. This research confirmed that enhanced biliary excretion, following chronic dieldrin exposure, was not explained by induction of xenobiotic metabolizing enzymes. The results are consistent with induction of hepatic intracellular trafficking proteins in dieldrin-fed fish.

  3. Does lindane (gamma-hexachlorocyclohexane) increase the rapid delayed rectifier outward K+ current (IKr) in frog atrial myocytes?

    OpenAIRE

    Sauviat, Martin-Pierre; Colas, Anthony; Pages, Nicole

    2002-01-01

    BACKGROUND: The effects of lindane, a gamma-isomer of hexachlorocyclohexane, were studied on transmembrane potentials and currents of frog atrial heart muscle using intracellular microelectrodes and the whole cell voltage-clamp technique. RESULTS: Lindane (0.34 microM to 6.8 microM) dose-dependently shortened the action potential duration (APD). Under voltage-clamp conditions, lindane (1.7 microM) increased the amplitude of the outward current (Iout) which developed in Ringer solution contain...

  4. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells.

    Science.gov (United States)

    Ghotbaddini, Maryam; Powell, Joann B

    2015-07-06

    The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR) expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models.

  5. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maryam Ghotbaddini

    2015-07-01

    Full Text Available The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR. TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models.

  6. Effect of trace dioxin(TCDD) uptake on medaka juvenile spine development%一次性微量二恶英(TCDD)摄取对青鳉幼鱼脊椎发育的影响

    Institute of Scientific and Technical Information of China (English)

    于永利; 魏素香; 董武

    2013-01-01

    The dioxin (TCDD) is a persistent environmental pollutants, its high residue and teratogenicity has attracted great attention in the world. Using medaka embryos as experimental animal model, the mechanism of TCDD toxicity on medaka embryo spine was explored from molecular level. The results showed that:TCDD caused a medaka juvenile spine formation disorder, and the spine number was negatively correlated with TCDD concentrations. TCDD also caused changes in embryonic cartilage development in medaka, and closely related with the decreased expression of Sox9b.%二恶英(TCDD)是一种持久性环境污染物质,它的高残留性、致畸性已经引起世界各国的重视.以青鳉胚胎作为试验动物模型,从分子水平探讨了TCDD对青鳉胚胎脊椎的毒性作用机制.结果表明:TCDD造成青鳉幼鱼脊椎生成障碍,脊椎生成数目与TCDD染毒浓度呈负相关.TCDD引起青鳉胚胎软骨发育的变化与Sox9b的表达降低密切相关.

  7. Insulin sensitivity and serum TCDD in Air Force veterans occupationally exposed to herbicides during the Vietnam war

    Energy Technology Data Exchange (ETDEWEB)

    Kern, P.; Said, S. [Univ. of Arkansas for Medical Sciences, Little Rock (United States); Jackson, W. Jr; Michalek, J. [Air Force Research Lab., San Antonio (United States)

    2004-09-15

    Between 1961 and 1971, the United States Air Force sprayed 12 million gallons of the defoliant ''Agent Orange'' on 3.6 million acres of Vietnam. Agent Orange was a 1:1 mixture of 2,4-dichlorophenoxyacetic acid and 2,4,5- trichlorophenoxyacetic acid, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was a contaminant of the defoliant, from less than 0.05 to almost 50 parts per million. Numerous Vietnam veterans were exposed to TCDD when Agent Orange and other TCDD-contaminated herbicides were sprayed in large quantities in Vietnam and TCDD has been found at many toxic waste disposal sites in the United States. Some of the highest exposure to TCDD occurred in members of Operation Ranch Hand, the Air Force unit responsible for spraying herbicides from fix-wing aircraft in Vietnam. The Air Force Health Study (AFHS), an epidemiological study of Ranch Hand veterans, was launched in 1980 to address veteran concerns regarding Agent Orange exposure. A link between TCDD and diabetes has been demonstrated in several studies. Among the Ranch Hand veterans with high blood levels of TCDD, there was a significant increase in the prevalence of diabetes and a decrease in the age at which diabetes was diagnosed. In a study from Seveso, Italy, where 45,000 people had varying levels of exposure to TCDD, there were significant increases in mortality from coronary artery disease and diabetes. Several studies have demonstrated a relationship between blood TCDD levels and hyperinsulinemia. The data suggest that non-diabetic individuals exposed to TCDD have an increased risk of insulin-resistance, being able to maintain normal blood glucose levels but only because of very high concentrations of insulin. As a result of available evidence, public policy decisions have been made, such as a decision by the Veterans Administration that diabetes is a service-connected condition in Agent Orange-exposed Vietnam veterans. Here we study the relation between TCDD insulin sensitivity

  8. Compound specific stable isotope analysis (CSIA) to characterize transformation mechanisms of α-hexachlorocyclohexane

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ning; Bashir, Safdar [Department of Isotope Biogeochemistry, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig (Germany); Qin, Jinyi [Department of Environmental Microbiology, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig (Germany); Schindelka, Janine [Department of Chemistry, Leibniz Institute for Tropospheric Research (TROPOS), Permoserstraße 15, 04318 Leipzig (Germany); Fischer, Anko [Department of Isotope Biogeochemistry, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig (Germany); Isodetect—Company for Isotope Monitoring, Deutscher Platz 5b, 04103 Leipzig (Germany); Nijenhuis, Ivonne [Department of Isotope Biogeochemistry, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig (Germany); Herrmann, Hartmut [Department of Chemistry, Leibniz Institute for Tropospheric Research (TROPOS), Permoserstraße 15, 04318 Leipzig (Germany); Wick, Lukas Y. [Department of Environmental Microbiology, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig (Germany); Richnow, Hans H., E-mail: hans.richnow@ufz.de [Department of Isotope Biogeochemistry, Helmholtz Centre for Environmental Research-UFZ, Permoserstraße 15, 04318 Leipzig (Germany)

    2014-09-15

    Highlights: • Isotope fractionation to investigate the mode of chemical reactions of α-HCH. • Characterization of the mode of reaction mechanisms using AKIE{sub C}. • Comparison of chemical and biological reaction mechanisms. • ESIA is feasible for identifying chemical and biological in situ transformations. - Abstract: A systematic investigation of environmentally relevant transformation processes of alpha-hexachlorocyclohexane (α-HCH) was performed in order to explore the potential of compound specific stable isotope analysis (CSIA) to characterize reaction mechanisms. The carbon isotope enrichment factors (ε{sub C}) for the chemical transformations of α-HCH via direct photolysis, indirect photolysis (UV/H{sub 2}O{sub 2}), hydrolysis, electro-reduction or reduction by Fe{sup 0} were quantified and compared to those previously published for biodegradation. Hydrogen abstraction by hydroxyl radicals generated by UV/H{sub 2}O{sub 2} led to ε{sub C} of −1.9 ± 0.2‰ with an apparent kinetic carbon isotope effect (AKIE{sub C}) of 1.012 ± 0.001. Dehydrochlorination by alkaline hydrolysis yielded ε{sub C} of −7.6 ± 0.4‰ with AKIE{sub C} of 1.048 ± 0.003. Dechlorination either by homolytic bond cleavage in direct photolysis (ε{sub C} = −2.8 ± 0.2‰) or single-electron transfer in electro-reduction (ε{sub C} = −3.8 ± 0.4‰) corresponded to AKIE{sub C} of 1.017 ± 0.001 and 1.023 ± 0.003, respectively. Dichloroelimination catalyzed by Fe{sup 0} via two-electron transfers resulted in ε{sub C} of −4.9 ± 0.1‰. AKIE{sub C} values assuming either a concerted or a stepwise mechanism were 1.030 ± 0.0006 and 1.015 ± 0.0003, respectively. Contrary to biodegradation, no enantioselectivity of α-HCH was observed in chemical reactions, which might be used to discriminate chemical and biological in situ transformations.

  9. Transport and fate of hexachlorocyclohexanes in the oceanic air and surface seawater

    Directory of Open Access Journals (Sweden)

    Z. Xie

    2011-06-01

    Full Text Available Hexachlorocyclohexanes (HCHs are ubiquitous organic pollutants derived from pesticide application. They are subject to long-range transport, persistent in the environment, and capable of accumulation in biota. Shipboard measurements of HCH isomers (α-, γ- and β-HCH in surface seawater and boundary layer atmospheric samples were conducted in the Atlantic and the Southern Ocean in October to December of 2008. ΣHCHs concentrations (the sum of α-, γ- and β-HCH in the lower atmosphere ranged from 11.8 to 36.9 pg m−3 (mean: 26.6 ± 11.0 pg m−3 in the Northern Hemisphere (NH, and from 1.5 to 4.0 pg m−3 (mean: 2.8 ± 1.1 pg m−3 in the Southern Hemisphere (SH, respectively. Water concentrations were: α-HCH 0.33–46.8 pg l−1, γ-HCH 0.02–33.2 pg l−1 and β-HCH 0.11–2 pg l−1. HCH concentrations decreased from the North Atlantic to the Southern Ocean, indicating historical use of HCHs in the NH. Spatial distribution showed increasing concentrations from the equator towards North and South latitudes illustrating the concept of cold condensation and less interhemispheric mixing process. In comparison to concentrations measured in 1987–1999/2000, gaseous HCHs were slightly lower, while dissolved HCHs decreased by factor of 2–3 orders of magnitude. Air-water exchange gradients suggested net deposition for α-HCH (mean: 3759 pg m−2 day−1 and γ-HCH (mean: 1987 pg m−2 day−1, whereas β-HCH varied between equilibrium (volatilization: <0–12 pg m−2 day−1 and net deposition (range: 6–687 pg m−2 day−1, indicating a multi-hopper transport behavior. Climate change may significantly accelerate the releasing process of "old" HCHs from continental storage (e.g. soil, vegetation and high mountains and drive long-range transport from sources to deposition in the

  10. Enhanced biodegradation of hexachlorocyclohexane (HCH) in contaminated soils via inoculation with Sphingobium indicum B90A.

    Science.gov (United States)

    Raina, Vishakha; Suar, Mrutyunjay; Singh, Ajaib; Prakash, Om; Dadhwal, Mandeep; Gupta, Sanjay Kumar; Dogra, Charu; Lawlor, Kirsten; Lal, Sukanya; van der Meer, Jan Roelof; Holliger, Christof; Lal, Rup

    2008-02-01

    Soil pollution with hexachlorocyclohexane (HCH) has caused serious environmental problems. Here we describe the targeted degradation of all HCH isomers by applying the aerobic bacterium Sphingobium indicum B90A. In particular, we examined possibilities for large-scale cultivation of strain B90A, tested immobilization, storage and inoculation procedures, and determined the survival and HCH-degradation activity of inoculated cells in soil. Optimal growth of strain B90A was achieved in glucose-containing mineral medium and up to 65% culturability could be maintained after 60 days storage at 30 degrees C by mixing cells with sterile dry corncob powder. B90A biomass produced in water supplemented with sugarcane molasses and immobilized on corncob powder retained 15-20% culturability after 30 days storage at 30 degrees C, whereas full culturability was maintained when cells were stored frozen at -20 degrees C. On the contrary, cells stored on corncob degraded gamma-HCH faster than those that had been stored frozen, with between 15 and 85% of gamma-HCH disappearance in microcosms within 20 h at 30 degrees C. Soil microcosm tests at 25 degrees C confirmed complete mineralization of [(14)C]-gamma-HCH by corncob-immobilized strain B90A. Experiments conducted in small pits and at an HCH-contaminated agricultural site resulted in between 85 and 95% HCH degradation by strain B90A applied via corncob, depending on the type of HCH isomer and even at residual HCH concentrations. Up to 20% of the inoculated B90A cells survived under field conditions after 8 days and could be traced among other soil microorganisms by a combination of natural antibiotic resistance properties, unique pigmentation and PCR amplification of the linA genes. Neither the addition of corncob nor of corncob immobilized B90A did measurably change the microbial community structure as determined by T-RFLP analysis. Overall, these results indicate that on-site aerobic bioremediation of HCH exploiting the

  11. Field estimates of polyurethane foam - air partition coefficients for hexachlorobenzene, alpha-hexachlorocyclohexane and bromoanisoles.

    Science.gov (United States)

    Bidleman, Terry F; Nygren, Olle; Tysklind, Mats

    2016-09-01

    Partition coefficients of gaseous semivolatile organic compounds (SVOCs) between polyurethane foam (PUF) and air (KPA) are needed in the estimation of sampling rates for PUF disk passive air samplers. We determined KPA in field experiments by conducting long-term (24-48 h) air sampling to saturate PUF traps and shorter runs (2-4 h) to measure air concentrations. Sampling events were done at daily mean temperatures ranging from 1.9 to 17.5 °C. Target compounds were hexachlorobenzene (HCB), alpha-hexachlorocyclohexane (α-HCH), 2,4-dibromoanisole (2,4-DiBA) and 2,4,6-tribromoanisole (2,4,6-TriBA). KPA (mL g(-1)) was calculated from quantities on the PUF traps at saturation (ng g(-1)) divided by air concentrations (ng mL(-1)). Enthalpies of PUF-to-air transfer (ΔHPA, kJ mol(-1)) were determined from the slopes of log KPA/mL g(-1) versus 1/T(K) for HCB and the bromoanisoles, KPA of α-HCH was measured only at 14.3 to 17.5 °C and ΔHPA was not determined. Experimental log KPA/mL g(-1) at 15 °C were HCB = 7.37; α-HCH = 8.08; 2,4-DiBA = 7.26 and 2,4,6-TriBA = 7.26. Experimental log KPA/mL g(-1) were compared with predictions based on an octanol-air partition coefficient (log KOA) model (Shoeib and Harner, 2002a) and a polyparameter linear free relationship (pp-LFER) model (Kamprad and Goss, 2007) using different sets of solute parameters. Predicted KP values varied by factors of 3 to over 30, depending on the compound and the model. Such discrepancies provide incentive for experimental measurements of KPA for other SVOCs.

  12. Impacts of TCDD and MeHg on DNA methylation in zebrafish (Danio rerio) across two generations.

    Science.gov (United States)

    Olsvik, Pål A; Williams, Timothy D; Tung, Hui-shan; Mirbahai, Leda; Sanden, Monica; Skjaerven, Kaja H; Ellingsen, Ståle

    2014-09-01

    This study aimed to investigate whether dioxin (TCDD) and methylmercury (MeHg) pose a threat to offspring of fish exposed to elevated concentrations of these chemicals via epigenetic-based mechanisms. Adult female zebrafish were fed diets added either 20 μg/kg 2,3,7,8 TCDD or 10 mg/kg MeHg for 47 days, or 10 mg/kg 5-aza-2'-deoxycytidine (5-AZA), a hypomethylating agent, for 32 days, and bred with unexposed males in clean water to produce F1 and F2 offspring. Global DNA methylation, promoter CpG island methylation and target gene transcription in liver of adult females and in 3 days post fertilization (dpf) F1 and F2 embryos were determined with HPLC, a novel CpG island tiling array containing 54,933 different probes and RT-qPCR, respectively. The results showed that chemical treatment had no significant effect on global DNA methylation levels in F1 (MeHg and TCDD) and F2 (MeHg) embryos and only a limited number of genes were identified with altered methylation levels at their promoter regions. CYP1A1 transcription, an established marker of TCDD exposure, was elevated 27-fold in F1 embryos compared to the controls, matching the high levels of CYP1A1 expression observed in F0 TCDD-treated females. This suggests that maternal transfer of TCDD is a significant route of exposure for the F1 offspring. In conclusion, the selected doses of TCDD and MeHg, two chemicals often found in high concentrations in fish, appear to have only modest effects on DNA methylation in F1 (MeHg and TCDD) and F2 (MeHg) embryos of treated F0 females.

  13. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice.

    Science.gov (United States)

    Lefever, Daniel E; Xu, Joella; Chen, Yingjia; Huang, Guannan; Tamas, Nagy; Guo, Tai L

    2016-08-01

    An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4×50mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3(+)NK(+) T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure.

  14. Behaviour of {alpha}-, {beta}-, {gamma}-, and {delta}-hexachlorocyclohexane in the soil-plant system of a contaminated site

    Energy Technology Data Exchange (ETDEWEB)

    Calvelo Pereira, R. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain)]. E-mail: edrobert@usc.es; Camps-Arbestain, M. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Rodriguez Garrido, B. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Macias, F. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Monterroso, C. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain)

    2006-11-15

    The behaviour of the organochlorine pesticide hexachlorocyclohexane (HCH) is investigated. The concentrations of {alpha}-, {beta}-, {gamma}-, and {delta}-HCH isomers were measured in soils, rhizosphere and vegetation in a contaminated area in Galicia (NW Spain). The total concentration of HCH in soils reached values close to 20 000 mg kg{sup -1}. The plants analysed (Avena sativa L., Chenopodium spp., Solanum nigrum L., Cytisus striatus (Hill) Roth, and Vicia sativa L.) accumulated HCH, especially the {beta}-HCH isomer, in their tissues. The most likely mechanisms of HCH accumulation in plants were sorption of soil HCH on roots and sorption of volatilized HCH on aerial plant tissues. The concentrations of HCH obtained from the bulk and rhizosphere soils of selected plant species suggest that roots tend to reduce levels of the HCH isomers in the rhizosphere. The results reflect the importance of vegetation in the distribution of organochlorine compounds in the soil-plant system. - This paper describes the soil-plant relationship of hexachlorocyclohexane isomers in a contaminated site, with special focus on the rhizosphere effect.

  15. Isolation and identification of dieldrin-degrading Pseudonocardia sp. strain KSF27 using a soil-charcoal perfusion method with aldrin trans-diol as a structural analog of dieldrin.

    Science.gov (United States)

    Sakakibara, Futa; Takagi, Kazuhiro; Kataoka, Ryota; Kiyota, Hiromasa; Sato, Yuuki; Okada, Sanae

    2011-07-22

    We isolated a novel aerobic dieldrin-degrading bacterium from an enrichment culture in a soil-charcoal perfusion system. Enrichment culture using a soil-charcoal perfusion system was an effective way to obtain microorganisms that degrade recalcitrant compounds. The soil-charcoal perfusion was performed using aldrin trans-diol, which was a metabolite of dieldrin. Aldrin trans-diol had higher bioavailability (2.5 mg/l) than dieldrin (0.1-0.25 mg/l), therefore it is possible for microorganisms to utilize it as a substrate in soil. After 100 days of circulation and three exchanges of the medium, the enriched charcoal was harvested and a bacterium isolated. The isolate was designated as strain KSF27 and was found to be closely related to Pseudonocardia spp. as determined by 16S rRNA sequencing analysis. Strain KSF27 degraded aldrin trans-diol by 0.05 μmol/l from an initial concentration of 25.5 μmol/l. The metabolite of aldrin trans-diol was detected by HPLC/MS and determined to be aldrindicarboxylic acid based on retention time and the MS fragment. Moreover, strain KSF27 degraded dieldrin from 14.06 μmol/l to 2.01 μmol/l over a 10-day incubation at 30°C. This strain degraded dieldrin and other persistent organochlorine pesticides, such as α-endosulfan, β-endosulfan, endosulfan sulfate, heptachlor, heptachlor epoxide and chlordecone. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Excitatory and depressant effects of dieldrin and aldrin-transdiol in the spinal cord of the toad (Xenopus laevis)

    NARCIS (Netherlands)

    Akkermans, L.M.A.; Bercken, J. van den; Versluijs-Helder, M.

    An investigation was made into the action of the insecticide dieldrin and one of its metabolites, aldrin-transdiol, on the isolated spinal cord of the toad, Xenopus laevis. Conventional electrophysiological techniques were used for stimulating and recording of dorsal and ventral spinal roots. An

  17. The pesticide dieldrin disrupts proteins related to oxidative respiration and mitochondrial stress in the central nervous system.

    Science.gov (United States)

    Cowie, Andrew M; Sarty, Kathleena I; Mercer, Angella; Koh, Jin; Kidd, Karen A; Martyniuk, Christopher J

    2017-04-01

    Quantitative proteins analysis was carried out in the hypothalamus of zebrafish following dietary exposure to the legacy pesticide dieldrin. Data were collected using iTRAQ labeling methodology and data were acquired using a hybrid quadrupole Orbitrap (Q Exactive) MS system (Thermo Fisher Scientific, Bremen, Germany). There were 3941 proteins identified in the hypothalamus of zebrafish, and these proteins comprised 23 unique expression patterns for proteins based on the three doses of dieldrin. There were 226 proteins that were regulated in one or more doses of dieldrin and 3715 proteins that were not affected. Thus, 5.7% of the proteins detected responded to the treatment. Many proteins that were differentially expressed were those found in, or associated with, the mitochondria. The proteomics data described in this article is associated with a research article, "Transcriptomic and proteomic analysis implicates the immune system and mitochondria as molecular targets of dieldrin in the zebrafish (Danio rerio) central nervous system" (A.M. Cowie, K.I. Sarty, A. Mercer, J. Koh, K.A. Kidd, C.J. Martyniuk, submitted) [1], and serves as a resource for researchers working in the field of pesticide exposures and protein biomarkers.

  18. The pesticide dieldrin disrupts proteins related to oxidative respiration and mitochondrial stress in the central nervous system

    Directory of Open Access Journals (Sweden)

    Andrew M. Cowie

    2017-04-01

    Full Text Available Quantitative proteins analysis was carried out in the hypothalamus of zebrafish following dietary exposure to the legacy pesticide dieldrin. Data were collected using iTRAQ labeling methodology and data were acquired using a hybrid quadrupole Orbitrap (Q Exactive MS system (Thermo Fisher Scientific, Bremen, Germany. There were 3941 proteins identified in the hypothalamus of zebrafish, and these proteins comprised 23 unique expression patterns for proteins based on the three doses of dieldrin. There were 226 proteins that were regulated in one or more doses of dieldrin and 3715 proteins that were not affected. Thus, 5.7% of the proteins detected responded to the treatment. Many proteins that were differentially expressed were those found in, or associated with, the mitochondria. The proteomics data described in this article is associated with a research article, “Transcriptomic and proteomic analysis implicates the immune system and mitochondria as molecular targets of dieldrin in the zebrafish (Danio rerio central nervous system” (A.M. Cowie, K.I. Sarty, A. Mercer, J. Koh, K.A. Kidd, C.J. Martyniuk, submitted [1], and serves as a resource for researchers working in the field of pesticide exposures and protein biomarkers.

  19. Adsorption of TCDD molecule onto CNTs and BNNTs: Ab initio van der Waals density-functional study

    Science.gov (United States)

    Darvish Ganji, M.; Alinezhad, H.; Soleymani, E.; Tajbakhsh, M.

    2015-03-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCCD) is one of the most dangerous compounds that infect the environment and hence its removal is crucial for safety in human life. In this work, we have investigated the interaction of TCDD with boron nitride nanotubes (BNNTs) and carbon nanotubes (CNTs) by using the density functional theory (DFT) calculations. Our first-principles results have been validated by experiment and also other theoretical values for the similar system. The adsorption energies for TCDD molecule on the BNNTs and CNT are calculated. It was found that TCDD adsorption ability of BNNT is slightly stronger than that of CNT and TCDD molecule prefers to be adsorbed on BNNTs with molecular axis parallel to the tube axis. The results obtained indicate that TCDD is weakly bound to the outer surface of all the considered nanotubes and the obtained adsorption energy values and binding distance are typical for the physisorption. We also evaluated the influence of curvature and introduced defects on the TCDD adsorption ability of BNNTs. Furthermore, we have analyzed the electronic structure and charge population for the energetically most favorable complexes and the results indicate that no significant hybridization between the respective orbitals of the two entities was accomplished.

  20. Dieldrin induces ubiquitin-proteasome dysfunction in alpha-synuclein overexpressing dopaminergic neuronal cells and enhances susceptibility to apoptotic cell death.

    Science.gov (United States)

    Sun, Faneng; Anantharam, Vellareddy; Latchoumycandane, Calivarathan; Kanthasamy, Arthi; Kanthasamy, Anumantha G

    2005-10-01

    Exposure to pesticides is implicated in the etiopathogenesis of Parkinson's disease (PD). The organochlorine pesticide dieldrin is one of the environmental chemicals potentially linked to PD. Because recent evidence indicates that abnormal accumulation and aggregation of alpha-synuclein and ubiquitin-proteasome system dysfunction can contribute to the degenerative processes of PD, in the present study we examined whether the environmental pesticide dieldrin impairs proteasomal function and subsequently promotes apoptotic cell death in rat mesencephalic dopaminergic neuronal cells overexpressing human alpha-synuclein. Overexpression of wild-type alpha-synuclein significantly reduced the proteasomal activity. Dieldrin exposure dose-dependently (0-70 microM) decreased proteasomal activity, and 30 microM dieldrin inhibited activity by more than 60% in alpha-synuclein cells. Confocal microscopic analysis of dieldrin-treated alpha-synuclein cells revealed that alpha-synuclein-positive protein aggregates colocalized with ubiquitin protein. Further characterization of the aggregates with the autophagosomal marker mondansyl cadaverine and the lysosomal marker and dot-blot analysis revealed that these protein oligomeric aggregates were distinct from autophagosomes and lysosomes. The dieldrin-induced proteasomal dysfunction in alpha-synuclein cells was also confirmed by significant accumulation of ubiquitin protein conjugates in the detergent-insoluble fraction. We found that proteasomal inhibition preceded cell death after dieldrin treatment and that alpha-synuclein cells were more sensitive than vector cells to the toxicity. Furthermore, measurement of caspase-3 and DNA fragmentation confirmed the enhanced sensitivity of alpha-synuclein cells to dieldrin-induced apoptosis. Together, our results suggest that increased expression of alpha-synuclein predisposes dopaminergic cells to proteasomal dysfunction, which can be further exacerbated by environmental exposure to certain

  1. Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations

    OpenAIRE

    Mohan Manikkam; Rebecca Tracey; Carlos Guerrero-Bosagna; Skinner, Michael K.

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease...

  2. Histopathological and Ultrastructural Studies of Liver Tissue from TCDD-Exposed Beach Mice (Peromyscus polionotus).

    Science.gov (United States)

    1980-03-01

    gross developmental .7so-i defects such as cleft palate , cleft lip and polydactyly. Body and organ weights were recorded, internal organs were examined...according to the study, sex and treatment , placed in glass jars, frozed and subnitted for TCDD analysis. Hepatic Ultrastructural Study After the liver was...weights per se was not attempted since the ages of the beach mice were not known and the animals could only be classified by sex and treatment . The

  3. Responsiveness of 6 to 14 generations of birds to dietary dieldrin toxicity

    Science.gov (United States)

    Hill, E.F.; Spann, J.W.; Williams, J.D.

    1977-01-01

    The lethal dietary toxicity of dieldrin was estimated repeatedly during 8 years of testing young bobwhites (Colinus virginianus), Japanese quail (Coturnix c. japonica), ring-necked pheasants (Phasianus colchicus), and mallards (Anas platyrhynchos). Toxicities, quantified as 8-day LC50 values (5 days on toxic diet, followed by 3 days of untreated feed), were estimated at least 18 times per species. Average dietary LC50 values (ppm) and their 95% confidence limits for 14-day-old quail and 10-day-old pheasants and mallards were: bobwhite, 38 (34?42); Japanese quail, 61 (58?64); ring-necked pheasant, 56 (53?59); and mallard, 179 (163?195). No time-related changes were detected in LC50 values for any of the species.

  4. Developmental neurotoxicants target neurodifferentiation into the serotonin phenotype: Chlorpyrifos, diazinon, dieldrin and divalent nickel.

    Science.gov (United States)

    Slotkin, Theodore A; Seidler, Frederic J

    2008-12-01

    Developmental exposure to organophosphates (OP) produces long-term changes in serotonin (5HT) synaptic function and associated behaviors, but there are disparities among the different OPs. We contrasted effects of chlorpyrifos and diazinon, as well as non-OP neurotoxicants (dieldrin, Ni(2+)) using undifferentiated and differentiating PC12 cells, a well-established neurodevelopmental model. Agents were introduced at 30 microM for 24 or 72 h, treatments devoid of cytotoxicity, and we evaluated the mRNAs encoding the proteins for 5HT biosynthesis, storage and degradation, as well as 5HT receptors. Chlorpyrifos and diazinon both induced tryptophan hydroxylase, the rate-limiting enzyme for 5HT biosynthesis, but chlorpyrifos had a greater effect, and both agents suppressed expression of 5HT transporter genes, effects that would tend to augment extracellular 5HT. However, whereas chlorpyrifos enhanced the expression of most 5HT receptor subtypes, diazinon evoked overall suppression. Dieldrin evoked even stronger induction of tryptophan hydroxylase, and displayed a pattern of receptor effects similar to that of diazinon, even though they come from different pesticide classes. In contrast, Ni(2+) had completely distinct actions, suppressing tryptophan hydroxylase and enhancing the vesicular monoamine transporter, while also reducing 5HT receptor gene expression, effects that would tend to lower net 5HT function. Our findings provide some of the first evidence connecting the direct, initial mechanisms of developmental neurotoxicant action on specific transmitter pathways with their long-term effects on synaptic function and behavior, while also providing support for in vitro test systems as tools for establishing mechanisms and outcomes of related and unrelated neurotoxicants.

  5. Applicability of the TCDD-TEQ approach to predict sublethal embryotoxicity in Fundulus heteroclitus.

    Science.gov (United States)

    Rigaud, Cyril; Couillard, Catherine M; Pellerin, Jocelyne; Légaré, Benoît; Hodson, Peter V

    2014-04-01

    The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent quantity (TCDD-TEQ) approach was used successfully to predict lethal embryotoxicity in salmonids, but its applicability to sublethal effects of mixtures of organohalogenated compounds in other fish species is poorly known. The sublethal toxicity of two dioxin-like compounds (DLCs), 3,3',4,4'-tetrachlorobiphenyl (PCB77) and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PnCDF), two non-dioxin-like (NDL) polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl (PCB52) and 2,3,3',4',6-pentachlorobiphenyl (PCB110), and of Aroclor 1254, a complex commercial mixture of PCBs, was assessed in Fundulus heteroclitus embryos exposed by intravitelline injection. At 16 days post-fertilization, the two DLCs and Aroclor 1254 altered prey capture ability in addition to inducing classical aryl hydrocarbon receptor-mediated responses: ethoxyresorufin-O-deethylase (EROD) induction, craniofacial deformities and reduction in body length. None of these responses was induced by the two NDL PCBs, at doses up to 5400 ng g(-1)wet weight. Dose-response curves for prey capture ability for the 2 DLCs tested were not parallel to that of TCDD, violating a fundamental assumption for relative potency (ReP) estimation. Dose-response curves for EROD induction were parallel for 2,3,4,7,8-PnCDF and TCDD, but the ReP of 2,3,4,7,8-PnCDF for F. heteroclitus was 5-fold higher than the World Health Organization (WHO) fish toxic equivalent factor (TEF) based on embryolethality in salmonids. The chemically derived TCDD-TEQs of Aroclor 1254, calculated using 3,3',4,4',5-pentachlorobiphenyl (PCB126) concentrations and it ReP for F. heteroclitus, overestimated its potency to induce EROD activity possibly due to antagonistic interactions among PCBs. This study highlights the limitations of using TEFs based on salmonid toxicity data alone for risk assessment to other fish species. There is a need to assess the variability of RePs of DLCs in

  6. TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin.

    Science.gov (United States)

    De Abrew, K Nadira; Thomas-Virnig, Christina L; Rasmussen, Cathy A; Bolterstein, Elyse A; Schlosser, Sandy J; Allen-Hoffmann, B Lynn

    2014-05-01

    The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial-stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin.

  7. Antioxidant compounds in the seaweed Gelidiella acerosa protects human Peripheral Blood Mononuclear Cells against TCDD induced toxicity.

    Science.gov (United States)

    Ilavarasi, K; Chermakani, P; Arif Nisha, S; Sheeja Malar, D; Pandima Devi, K

    2015-04-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental toxin formed as an unintentional by-product of incomplete combustion. Several therapeutic approaches have evolved to combat its toxicity since it elicits immunotoxicity, neurotoxicity, hepatotoxicity, carcinogenicity and lethality. Search for drugs from natural resources especially from seaweeds has become intense due to their enormous pharmacological potential. Hence, the present study aims at revealing the protective effect of methanolic extract of G. acerosa (MEGA) in Peripheral Blood Mononuclear Cells (PBMC) against TCDD induced toxicity, by assessing the antioxidant, anti-apoptotic and cytoprotective activities. The results of antioxidant assays suggests that MEGA reverted TCDD induced toxicity by causing an alteration in the levels of antioxidant enzymes (Catalase [CAT], Superoxide dismutase [SOD], Glutathione peroxidase [GPx], Glutathione-S-transferase [GST]) and Glutathione [GSH]. The results of lipid peroxidation assay and protein carbonyl content reveal that MEGA protects PBMC from TCDD induced macromolecular damage. MEGA was found to exhibit significant (p TCDD induced oxidative DNA damage. Levels of phase-I detoxification enzymes determined by EROD assay and semi-quantitative RT-PCR showed that TCDD up-regulates the expression of CYP1A1 and upon co-treatment with MEGA, the expression got slightly decreased suggesting its protective role. Preliminary phytochemical analysis demonstrates that the extract is rich in cardiac glycosides and terpenoids. LC-MS analysis revealed the presence of antioxidants including caffeic acid, phytol and mannoheptulose in MEGA, which could be attributed for the observed protective effect against TCDD induced toxicity.

  8. Behaviour of alpha-, beta-, gamma-, and delta-hexachlorocyclohexane in the soil-plant system of a contaminated site.

    Science.gov (United States)

    Calvelo Pereira, R; Camps-Arbestain, M; Rodríguez Garrido, B; Macías, F; Monterroso, C

    2006-11-01

    The behaviour of the organochlorine pesticide hexachlorocyclohexane (HCH) is investigated. The concentrations of alpha-, beta-, gamma-, and delta-HCH isomers were measured in soils, rhizosphere and vegetation in a contaminated area in Galicia (NW Spain). The total concentration of HCH in soils reached values close to 20,000 mgkg(-1). The plants analysed (Avena sativa L., Chenopodium spp., Solanum nigrum L., Cytisus striatus (Hill) Roth, and Vicia sativa L.) accumulated HCH, especially the beta-HCH isomer, in their tissues. The most likely mechanisms of HCH accumulation in plants were sorption of soil HCH on roots and sorption of volatilized HCH on aerial plant tissues. The concentrations of HCH obtained from the bulk and rhizosphere soils of selected plant species suggest that roots tend to reduce levels of the HCH isomers in the rhizosphere. The results reflect the importance of vegetation in the distribution of organochlorine compounds in the soil-plant system.

  9. Dieldrin induces apoptosis by promoting caspase-3-dependent proteolytic cleavage of protein kinase Cdelta in dopaminergic cells: relevance to oxidative stress and dopaminergic degeneration.

    Science.gov (United States)

    Kitazawa, M; Anantharam, V; Kanthasamy, A G

    2003-01-01

    We previously reported that dieldrin, one of the potential environmental risk factors for development of Parkinson's disease, induces apoptosis in dopaminergic cells by generating oxidative stress. Here, we demonstrate that the caspase-3-dependent proteolytic activation of protein kinase Cdelta (PKCdelta) mediates as well as regulates the dieldrin-induced apoptotic cascade in dopaminergic cells. Exposure of PC12 cells to dieldrin (100-300 microM) results in the rapid release of cytochrome C, followed by the activation of caspase-9 and caspase-3 in a time- and dose-dependent manner. The superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride significantly attenuates dieldrin-induced cytochrome C release, indicating that reactive oxygen species may contribute to the activation of pro-apoptotic factors. Interestingly, dieldrin proteolytically cleaves native PKCdelta into a 41 kDa catalytic subunit and a 38 kDa regulatory subunit to activate the kinase. The dieldrin-induced proteolytic cleavage of PKCdelta and induction of kinase activity are completely inhibited by pretreatment with 50-100 microM concentrations of the caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) and benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (Z-DEVD-FMK), indicating that the proteolytic activation of PKCdelta is caspase-3-dependent. Additionally, Z-VAD-FMK, Z-DEVD-FMK or the PKCdelta specific inhibitor rottlerin almost completely block dieldrin-induced DNA fragmentation. Because dieldrin dramatically increases (40-80-fold) caspase-3 activity, we examined whether proteolytically activated PKCdelta amplifies caspase-3 via positive feedback activation. The PKCdelta inhibitor rottlerin (3-20 microM) dose-dependently attenuates dieldrin-induced caspase-3 activity, suggesting positive feedback activation of caspase-3 by PKCdelta. Indeed, delivery of catalytically active recombinant PKCdelta via a protein delivery system significantly

  10. 2, 3, 7, 8-Tetrachlorodibenzo-P-dioxin (TCDD induces premature senescence in human and rodent neuronal cells via ROS-dependent mechanisms.

    Directory of Open Access Journals (Sweden)

    Chunhua Wan

    Full Text Available The widespread environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD is a potent toxicant that causes significant neurotoxicity. However, the biological events that participate in this process remain largely elusive. In the present study, we demonstrated that TCDD exposure triggered apparent premature senescence in rat pheochromocytoma (PC12 and human neuroblastoma SH-SY5Y cells. Senescence-associated β-galactosidase (SA-β-Gal assay revealed that TCDD induced senescence in PC12 neuronal cells at doses as low as 10 nM. TCDD led to F-actin reorganization and the appearance of an alternative senescence marker, γ-H2AX foci, both of which are important features of cellular senescence. In addition, TCDD exposure altered the expression of senescence marker proteins, such as p16, p21 and p-Rb, in both dose- and time-dependent manners. Furthermore, we demonstrated that TCDD promotes mitochondrial dysfunction and the accumulation of cellular reactive oxygen species (ROS in PC12 cells, leading to the activation of signaling pathways that are involved in ROS metabolism and senescence. TCDD-induced ROS generation promoted significant oxidative DNA damage and lipid peroxidation. Notably, treatment with the ROS scavenger N-acetylcysteine (NAC markedly attenuated TCDD-induced ROS production, cellular oxidative damage and neuronal senescence. Moreover, we found that TCDD induced a similar ROS-mediated senescence response in human neuroblastoma SH-SY5Y cells. In sum, these results demonstrate for the first time that TCDD induces premature senescence in neuronal cells by promoting intracellular ROS production, supporting the idea that accelerating the onset of neuronal senescence may be an important mechanism underlying TCDD-induced neurotoxic effects.

  11. 2, 3, 7, 8-Tetrachlorodibenzo-P-dioxin (TCDD) induces premature senescence in human and rodent neuronal cells via ROS-dependent mechanisms.

    Science.gov (United States)

    Wan, Chunhua; Liu, Jiao; Nie, Xiaoke; Zhao, Jianya; Zhou, Songlin; Duan, Zhiqing; Tang, Cuiying; Liang, Lingwei; Xu, Guangfei

    2014-01-01

    The widespread environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent toxicant that causes significant neurotoxicity. However, the biological events that participate in this process remain largely elusive. In the present study, we demonstrated that TCDD exposure triggered apparent premature senescence in rat pheochromocytoma (PC12) and human neuroblastoma SH-SY5Y cells. Senescence-associated β-galactosidase (SA-β-Gal) assay revealed that TCDD induced senescence in PC12 neuronal cells at doses as low as 10 nM. TCDD led to F-actin reorganization and the appearance of an alternative senescence marker, γ-H2AX foci, both of which are important features of cellular senescence. In addition, TCDD exposure altered the expression of senescence marker proteins, such as p16, p21 and p-Rb, in both dose- and time-dependent manners. Furthermore, we demonstrated that TCDD promotes mitochondrial dysfunction and the accumulation of cellular reactive oxygen species (ROS) in PC12 cells, leading to the activation of signaling pathways that are involved in ROS metabolism and senescence. TCDD-induced ROS generation promoted significant oxidative DNA damage and lipid peroxidation. Notably, treatment with the ROS scavenger N-acetylcysteine (NAC) markedly attenuated TCDD-induced ROS production, cellular oxidative damage and neuronal senescence. Moreover, we found that TCDD induced a similar ROS-mediated senescence response in human neuroblastoma SH-SY5Y cells. In sum, these results demonstrate for the first time that TCDD induces premature senescence in neuronal cells by promoting intracellular ROS production, supporting the idea that accelerating the onset of neuronal senescence may be an important mechanism underlying TCDD-induced neurotoxic effects.

  12. Development of toxic equivalency factors for PCB congeners and the assessment of TCDD and PCB mixtures in rainbow trout

    Science.gov (United States)

    Newsted, John L.; Jones, Paul D.; Giesy, John P.; Crawford, Robert A.; Ankley, Gerald T.; Tillitt, Donald E.; Gooch, Jay W.; Denison, Michael S.

    1995-01-01

    This study was undertaken to evaluate the relationship between mammalian and piscine 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalency factors (TEFs) for PCBs, based on induction of CYP1A enzyme activity, catalytic protein, and mRNA. Rainbow trout administered a single i.p. injection of TCDD had an average (±SD) ED50 of 0.91 ± 0.14 μg TCDD/kg for induction of ethoxyresorufin O-deethylase (EROD) activity. Ortho-substituted PCB congeners 2,3,3′,4,4′-pentachlorobiphenyl (PCB 105), 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118), 2,3,3′4,4′5-hexachlorobiphenyl (PCB !56), and 2,2′3,4,4′,5-hexachlorobiphenyl (PCB 138) did not induce CYP1A activity in rainbow trout. Only three non-ortho-substituted PCBs, i.e., 3,3′4,4′-tetrachlorobiphenyl (PCB 77), 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), and 3,3′4,4′5,5′-hexachlorobiphenyl (PCB 169) induced CYP1A enzyme activity, protein, and mRNA. The ED50s for induction of EROD activity were calculated as 134, 5.82, and 93.7 μg/kg for PCB 77, PCB 126, and PCB 169, respectively. The TCDD-TEFs based on EROD activity were 0.0006, 0.0014, and 0.0003 for PCB 77, PCB 126, and PCB 169, respectively. Binary mixtures of TCDD and three PCBs were also evaluated. Based on EROD activity and CYP1A protein, mixtures of TCDD and PCB 77 were slightly greater than additive. Mixtures of TCDD-PCB 156 and TCDD-PCB 126 were slightly less than additive. Results from these studies indicate that mammal-derived TEFs will underestimate the potency of planar chlorinated hydrocarbon mixtures to induce the CYP1A catalytic activity in rainbow trout. Also, while interactions among PCB congeners and TCDD were somewhat equivocal, they did not greatly differ from predicted additive responses.

  13. Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-inducible genes in human amniotic epithelial cells

    Directory of Open Access Journals (Sweden)

    Kokame Koichi

    2006-05-01

    Full Text Available Abstract Background Exposure to dioxins results in a broad range of pathophysiological disorders in human fetuses. In order to evaluate the effects of dioxins on the feto-placental tissues, we analyzed the gene expression in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD treated primary cultures of human amniotic epithelial cells. Methods Human amniotic epithelial cells were dispersed by trypsin from amniotic membranes and cultured in DME/Ham's F12 medium supplemented with 10% FBS. Two weeks after plating, cells were treated with 50 nM TCDD or DMSO (control, further incubated for 48 hrs, and the gene expression was analyzed by DNA microarray technology and quantitative real-time PCR. Results Thirty eight TCDD-inducible genes, including cytochromeP4501A1 and cytochromeP4501B1, were identified. One of the remarkable profiles of the gene expression was the prominent up-regulation of interferon-inducible genes. The genes involved in the interferon gene expression and interferon signaling pathways were also up-regulated. Furthermore, the expression of genes related to collagen synthesis or degradation was enhanced by TCDD. Conclusion Using DNA microarray and quantitative real-time PCR analyses, we identified TCDD-inducible genes, including interferon-inducible genes and genes related to collagen synthesis or degradation, in human amniotic epithelial cells.

  14. Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on intermediary metabolism in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lakshman, M.R.; Ghosh, P.; Chirtel, S.J. (V.A. Medical Center, Washington, DC (United States))

    1991-03-11

    The effects of three days of exposure to a single 20 {mu}g/kg dosage of TCDD on fat mobilization and the fates of the mobilized fatty acids and glycerol were determined. It was found that TCDD caused a significant mobilization of depot fat into the plasma compartment resulting in 1.5-2.8 fold increase in plasma free-fatty acid concentrations. The same treatment of TCDD caused a 32% inhibition of the rate of hepatic oleate oxidation to CO{sub 2} without significantly affecting the rate of fatty acid esterification to triglycerides. In contrast, hepatic ketogenic rate from oleate and octanoate was markedly stimulated by 85% and 69% respectively. These results support the concept that although the translocation of long chain fatty acids from the outer mitochondrial membrane into the inner mitochondrial membrane via the carnitine pathway and their subsequent beta-oxidation of the fatty acids must be working normally, their complete oxidation to CO{sub 2}via the TCA cycle is impaired. At the same time, TCDD seems to preferentially divert the acetyl CoA generated from the beta-oxidation of fatty acids to the ketogenic pathway. Surprisingly, TCDD treatment inhibited the hepatic ketogenic rate from glycerol by 21% and its oxidation by 31% without affecting its esterification.

  15. Development of a Model Immunoassay Utilizing Monoclonal Antibodies of Different Specificities for Quantitative Determination of Dieldrin and Heptachlors in Their Mixtures.

    Science.gov (United States)

    Kataoka, Chiwa; Nihei, Masumi; Nimata, Masaomi; Sawadaishi, Kazuyuki

    2016-11-23

    The presence of dieldrin and heptachlor residues in cucurbitaceous crops at concentrations exceeding the limits set by the Japanese Food Sanitation Law constitutes a serious problem. To prevent accumulation of these residues in cucurbitaceous crops, development of high-throughput analysis methods for the detection of contaminants in the soil before cultivation is required. This study aimed to develop a model immunoassay using new monoclonal antibodies (MAbs) to quantitatively determine dieldrin and heptachlor contents in their mixtures. Three distinctive MAbs were obtained from mice immunized with the respective immunogens. MAb DrA-04 showed high reactivity toward dieldrin with ca. 20% cross-reactivity toward heptachlors. MAb DrC-02 displayed a similar reactivity toward dieldrin and heptachlors. The specificity and sensitivity of MAbs DrA-04 and DrC-02 were largely unaffected by the composition ratio of heptachlors in a mixture. Six standard mixtures with different dieldrin and heptachlor contents were prepared. Concentrations of dieldrin and heptachlors in standard mixtures, calculated on the basis of an immunoassay with MAbs DrA-04 and DrC-02, were 88.1-125 and 96.2-115% of the theoretical values, respectively, revealing excellent sensitivity and specificity of this assay. The developed method paves the way for a facile and rapid quantitative determination of chlorinated cyclodiene pesticides in soil.

  16. TCDD1100大直径车轮热成形工艺的研究%Thermoforming Process of TCDD1100 Large Diameter Wheel

    Institute of Scientific and Technical Information of China (English)

    张磊; 杜云岗; 白恩泽

    2014-01-01

    TCDD1100车轮是我公司出口土耳其的产品,也是目前我公司出口产品中外径最大的车轮。该车轮结构复杂,即辐板薄且较长,车轮轮辋较重,热成形金属分布和流动相对复杂。%TCDDΦ1100 wheel is our export products in Turkey, also the largest outer diameter wheel for outlet. The wheel has complex structure. The spoke is a long but thin and the wheel rim is heavier. While hot rolling forming, metal distribution and flow is relatively complicated.

  17. Identification and distribution of a GABA receptor mutation conferring dieldrin resistance in the malaria vector Anopheles funestus in Africa.

    Science.gov (United States)

    Wondji, Charles S; Dabire, Roch K; Tukur, Zainab; Irving, Helen; Djouaka, Rousseau; Morgan, John C

    2011-07-01

    Growing problems of pyrethroid resistance in Anopheles funestus have intensified efforts to identify alternative insecticides. Many agrochemicals target the GABA receptors, but cross-resistance from dieldrin resistance may preclude their introduction. Dieldrin resistance was detected in An. funestus populations from West (Burkina Faso) and central (Cameroon) Africa, but populations from East (Uganda) and Southern Africa (Mozambique and Malawi) were fully susceptible to this insecticide. Partial sequencing of the dieldrin target site, the γ-aminobutyric acid (GABA) receptor, identified two amino acid substitutions, A296S and V327I. The A296S mutation has been associated with dieldrin resistance in other species. The V327I mutations was detected in the resistant sample from Burkina Faso and Cameroon and consistently associated with the A296S substitution. The full-length of the An. funestus GABA-receptor gene, amplified by RT-PCR, generated a sequence of 1674 bp encoding 557 amino acid of the protein in An. funestus with 98% similarity to that of Anopheles gambiae. Two diagnostic assays were developed to genotype the A296S mutation (pyrosequencing and PCR-RFLP), and use of these assays revealed high frequency of the resistant allele in Burkina Faso (60%) and Cameroon (82%), moderate level in Benin (16%) while low frequency or absence of the mutation was observed respectively in Uganda (7.5%) or 0% in Malawi and Mozambique. The distribution of the Rdl(R) mutation in An. funestus populations in Africa suggests extensive barriers to gene flow between populations from different regions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Proteomic Analysis of the Rat Ovary Following Chronic Low-Dose Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

    NARCIS (Netherlands)

    Chen, Xi; Ma, Xiao-ming; Ma, Shi-wei; Coenraads, Pieter-Jan; Zhang, Chun-mei; Liu, Jing; Zhao, Li-jun; Sun, Min; Tang, Nai-jun

    2009-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (2

  19. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on signal transduction pathway-related protein expression in liver and cerebrum of rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Mari; Akema, Satoshi; Tsuzuki, Masami; Kubota, Shunichiro [Tokyo Univ. (Japan); Korenaga, Tatsumi; Fukusato, Toshio [Teikyo Univ. of School of Medicine, Tokyo (Japan); Asaoka, Kazuo [Kyoto Univ. (Japan); Murata, Nobuo [Teikyo Univ. of School of Medicine, Kawasaki (Japan); Nomizu, Motoyoshi [Hokkaido Univ., Sapporo (Japan); Arima, Akihiro [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan)

    2004-09-15

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to produce a wide range of toxic and biochemical effects in experimental animals, including immunological dysfunctions, chloracne, tetragenecity and carcinogenesis. Recently, the potential impact of dioxins on neurological disorders with particular focus on attention deficit hyperactivity disorder (ADHD) are concerned. Although a lot of information is available from studies in rodents, not much is known of the low dose effects of TCDD in non-human primates. In higher animals, dioxins are metabolized slowly, as evidenced by the estimated TCDD half-life of 5.8 to 14.1 years. Therefore, it is necessary to investigate the long-term effects of TCDD on human health. Considering the pronounced species differences observed in some studies of TCDD, the studies using primates are needed for assessment of TCDD exposure on human health. We have been studying the metabolism and the effects of single administration of TCDD on pregnant monkey (F0) and F1 rhesus monkey. The focus of the present study is to study the effects of TCDD on signal transduction pathway-related protein levels in various organs, especially in liver and brain of F0 monkeys.

  20. Relationship between deer mouse population parameters and dieldrin contamination in the Rocky Mountain Arsenal National Wildlife Refuge

    Science.gov (United States)

    Allen, D.L.; Otis, D.L.

    1998-01-01

    A small-mammal capture-recapture study was conducted in the Rocky Mountain Arsenal National Wildlife Refuge to quantify the effects of soil contamination with dieldrin on demographic parameters of deer mouse (Peromyscus maniculatus) populations. Increased dieldrin concentrations were significantly associated with larger deer mouse populations, although the size of populations on contaminated sites decreased during the study. The most parsimonious model for estimating survival rates was one in which survival was a decreasing function of dieldrin concentration. A significantly higher proportion of female deer mice in the populations residing on the more highly contaminated sites exhibited signs of reproductive activity. Development of genetic resistance in P. maniculatus to chronic chemical exposure is suggested as a possible mechanism responsible for the species' observed dominance and relatively high densities on contaminated sites. Under the additional stress of unfavorable environmental conditions, however, these populations may suffer disproportionately greater mortality. The design and analytical methods presented offer a rigorous statistical approach to assessing the effects of environmental contamination on small mammals at the population level.

  1. RESIDU PESTISIDA ALDRIN DAN DIELDRIN PADA SAMPEL TANAH DAN AIR DI DESA SRIGADING KECAMATAN SANDEN KABUPATEN BANTUL

    Directory of Open Access Journals (Sweden)

    Iin Narwanti

    2013-11-01

    Full Text Available Aldrin and dieldrin pesticide residue in soil and water samples from Srigading Village, Sanden District, Bantul Regency has been investigated. The purpose of this study were to analyze, identificate and evaluate pyrethroid pesticide residues in soil and water samples. Soil sample was extracted using shaker with acetone solvent. Water samples was extracted using separator funnel with 15% (v/v dichloromethane/n-hexane solvent.Clean-up was couducted using chromatography column using florisil and determination of pesticide residue in the samples was carried out by gas chromatography apparatus equipped with electron capture detector (GC-ECD. The result showed that pesticide residues in soil sample in the range level: aldrin (4,8-64,8 ppb and dieldrin (not detected-6,0 ppb. In water sample pesticide residues in the range level: aldrin (not detected-1,0 ppb dan dieldrin (-not detected1,2 ppb. The quality or water sample taken from onion field is laid under the standard of water that has been settled.

  2. Oxidative and excitatory mechanisms of developmental neurotoxicity: transcriptional profiles for chlorpyrifos, diazinon, dieldrin, and divalent nickel in PC12 cells.

    Science.gov (United States)

    Slotkin, Theodore A; Seidler, Frederic J

    2009-04-01

    Oxidative stress and excitotoxicity underlie the developmental neurotoxicity of numerous chemicals. We compared the effects of organophosphates (chlorpyrifos and diazinon), an organo-chlorine (dieldrin), and a metal [divalent nickel (Ni2+)] to determine how these mechanisms contribute to similar or dissimilar neurotoxic outcomes. We used PC12 cells as a model of developing neurons and evaluated transcriptional profiles for genes for oxidative stress responses and glutamate receptors. Chlorpyrifos had a greater effect on oxidative-stress-related genes in differentiating cells compared with the undifferentiated state. Chlorpyrifos and diazinon showed significant concordance in their effects on glutathione-related genes, but they were negatively correlated for effects on catalase and superoxide dismutase isoforms and had no concordance for effects on ionotropic glutamate receptors. Surprisingly, the correlations were stronger between diazinon and dieldrin than between the two organophosphates. The effects of Ni2+ were the least similar for genes related to oxidative stress but had significant concordance with dieldrin for effects on glutamate receptors. Our results point to underlying mechanisms by which different organophosphates produce disparate neurotoxic outcomes despite their shared property as cholinesterase inhibitors. Further, apparently unrelated neurotoxicants may produce similar outcomes because of convergence on oxidative stress and excitotoxicity. The combined use of cell cultures and microarrays points to specific end points that can distinguish similarities and disparities in the effects of diverse developmental neurotoxicants.

  3. Analysis of transport and ground deposition of the TCDD emitted on 10 July 1976 from the ICMESA factory (Seveso, Italy)

    Science.gov (United States)

    Cavallaro, A.; Tebaldi, G.; Gualdi, R.

    The areas affected by the contamination of TCDD emitted by the ICMESA factory (Meda-Seveso, Italy) have been identified through soil samples. To determine the course of the paniculate toxic cloud, we have analysed the wind field considering the data obtained by the six meteorological stations placed in the vicinity of the factory. After determining the theoretical path of the release, we have studied the values of the ground concentration of TCDD and we have looked for a deposition equation. We thus demonstrated out that the axial deposition YCA( μgm-2) decreases exponentially accordingly to two different regression lines: YCA = 2900 exp(-2.3 x) forx TCDD deposition should tend to the value of 0.3 μg m -2: at a distance of 10 km from ICMESA and there later sampling showed a maximum value of 0.2μg m -2.

  4. Molecular networks related to the immune system and mitochondria are targets for the pesticide dieldrin in the zebrafish (Danio rerio) central nervous system.

    Science.gov (United States)

    Cowie, Andrew M; Sarty, Kathleena I; Mercer, Angella; Koh, Jin; Kidd, Karen A; Martyniuk, Christopher J

    2017-03-22

    The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides. Processes related to oxidative phosphorylation were also differentially affected by dieldrin. Quantitative proteomics (iTRAQ) using a hybrid quadrupole-Orbitrap identified 226 proteins that were different following one or more doses. These proteins included ATP synthase subunits (mitochondrial) and hypoxia up-regulated protein 1 which were decreased and NADH dehydrogenases (mitochondrial) and signal recognition particle 9 which were up-regulated. Thus, proteins affected were functionally associated with the mitochondria and a protein network analysis implicated Parkinson's disease (PD) and Huntington's disease as diseases associated with altered proteins. Molecular networks related to mitochondrial dysfunction and T-cell regulation are hypothesized to underlie the association between dieldrin and PD. These data contribute to a comprehensive transcriptomic and proteomic biomarker framework for pesticide exposures and neurodegenerative diseases. Dieldrin is a persistent organochlorine pesticide that has been associated with human neurodegenerative disease such as Parkinson's disease. Dieldrin is ranked 18th on the 2015 U.S. Agency for Toxic Substances and Disease Registry and continues to be a pesticide of concern for human health. Transcriptomics and quantitative proteomics (ITRAQ) were employed to characterize the molecular networks in the central nervous system that are

  5. Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD.

    OpenAIRE

    1994-01-01

    This study examined the changes in cellular glucose uptake induced by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) as measured by quantification of intracellular radioactivity in the NIH 3T3 L1 preadipocyte cell line after a 30-minute incubation with the non-metabolizable radioactive analogue of glucose, 3-O-methyl-D-[1-3H] glucose. Treatment of differentiated NIH 3T3 L1 cells with TCDD produced a time- and dose-dependent decrease in the cellular uptake of glucose. Treatment of cells for 3 hr w...

  6. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

    OpenAIRE

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G

    1993-01-01

    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses ...

  7. Toxicogenomic Evaluation of Long-term Hepatic Effects of TCDD in Immature, Ovariectomized C57BL/6 Mice

    OpenAIRE

    Kopec, Anna K; Boverhof, Darrell R.; Nault, Rance; Harkema, Jack R.; Tashiro, Colleen; Potter, Dave; Sharratt, Bonnie; Chittim, Brock; Zacharewski, Timothy R

    2013-01-01

    Acute exposure to hepatotoxic doses of 2,3,7,8-tetrachloro- dibenzo-p-dioxin (TCDD) in mice is characterized by differential gene expression that can be phenotypically anchored to elevated levels of serum alanine aminotransferase, increased relative liver weights, hepatic steatosis, inflammation, and hepatocellular necrosis. Unlike most studies that focus on acute exposure effects, this study evaluated the long-term effects of a single oral gavage of 30 μg/kg TCDD at 1, 4, 12, 24, 36, and 72 ...

  8. Circulating soluble CD27 and CD30 in workers exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Saberi Hosnijeh, Fatemeh; Portengen, Lützen; Bueno-de-Mesquita, H Bas; Heederik, Dick; Vermeulen, Roel

    2013-12-01

    Previous studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings remain inconclusive. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. In this cross-sectional study, we investigated changes in plasma levels of interleukin 1 receptor antagonist (IL1RA) and soluble (s)CD27 and sCD30 which have been found to be predictive of lymphoma, among workers of a cohort occupationally exposed to TCDD. Eighty-five workers who had been exposed to TCDD more than 30 years before blood collection were included in the current investigation. Plasma level of the markers was measured by ELISA. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high-resolution mass spectrometry. TCDD blood levels at time of last exposure were estimated using a one-compartment first order kinetic model. Exposure-response analyses showed no significant association between blood levels of sCD27, and sCD30 and current and estimated TCDD levels at time of last exposure. IL1RA showed a borderline significant decrease with increasing plasma TCDD levels (P = 0.07), which reached formal statistical significance when excluding subjects with chronic diseases. In conclusion, no clear dose-response relationship was observed between the measured markers and TCDD level. However, there was a suggestion that markers in particular IL1RA tended to decrease with increasing TCDD levels. This observation is consistent with our earlier observation on decreasing cytokine levels, suggesting immunosuppression, with increasing exposures. These findings possibly provide new insights in the etiology of NHL and the mechanisms through which TCDD can increase lymphoma risk.

  9. The effects of genetic manipulation, dieldrin treatment and irradiation on the mating competitiveness of male Anopheles arabiensis in field cages.

    Science.gov (United States)

    Yamada, Hanano; Vreysen, Marc J B; Gilles, Jeremie R L; Munhenga, Givemore; Damiens, David D

    2014-08-13

    To enable the release of only sterile male Anopheles arabiensis mosquitoes for the sterile insect technique, the genetic background of a wild-type strain was modified to create a genetic sexing strain ANO IPCL1 that was based on a dieldrin resistance mutation. Secondly, the eggs of ANO IPCL1 require treatment with dieldrin to allow complete elimination of female L1 larvae from the production line. Finally, male mosquito pupae need to be treated with an irradiation dose of 75 Gy for sterilization. The effects of these treatments on the competitiveness of male An. arabiensis were studied. The competitiveness of ANO IPCL1 males that were treated either with irradiation or both dieldrin and irradiation, was compared with that of the wild-type strain (An. arabiensis Dongola) at a 1:1 ratio in 5.36 m3 semi-field cages located in a climate-controlled greenhouse. In addition, three irradiated: untreated male ratios were tested in semi-field cages (1:1, 5:1 and 10:1) and their competition for virgin wild-type females was assessed. The ANO IPCL1 males were equally competitive as the wild-type males in this semi-field setting. The ANO IPCL1 males irradiated at 75 Gy were approximately half as competitive as the unirradiated wild-type males. ANO IPCL1 males that had been treated with dieldrin as eggs, and irradiated with 75 Gy as pupae were slightly more competitive than males that were only irradiated. Ratios of 1:1, 5:1 and 10:1 irradiated ANO IPCL1 males: untreated wild-type males resulted in 31, 66 and 81% induced sterility in the female cage population, respectively. An irradiation dose of 75 Gy reduced the competitiveness of male ANO IPCL1 significantly and will need to be compensated by releasing higher numbers of sterile males in the field. However, the dieldrin treatment used to eliminate females appears to have an unexpected radioprotectant effect, however the mechanism is not understood. A sterile to wild-type ratio of 10:1 effectively reduced the population

  10. Photochemical processing of aldrin and dieldrin in frozen aqueous solutions under arctic field conditions.

    Science.gov (United States)

    Rowland, Glenn A; Bausch, Alexandra R; Grannas, Amanda M

    2011-05-01

    Organochlorine (OC) contaminants are transported to the Polar Regions, where they have the potential to bioaccumulate, presenting a threat to the health of wildlife and indigenous communities. They deposit onto snowpack during winter, and accumulate until spring, when they experience prolonged solar irradiation until snowmelt occurs. Photochemical degradation rates for aldrin and dieldrin, in frozen aqueous solution made from MilliQ water, 500 μM hydrogen peroxide solution or locally-collected melted snow were measured in a field campaign near Barrow, AK, during spring-summer 2008. Significant photoprocessing of both pesticides occurs; the reactions depend on temperature, depth within the snowpack and whether the predominant phase is ice or liquid water. The effect of species present in natural snowpack is comparable to 500 μM hydrogen peroxide, pointing to the potential significance of snowpack-mediated reactions. Aldrin samples frozen at near 0 °C were more reactive than comparable liquid samples, implying that the microenvironments experienced on frozen ice surfaces are an important consideration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Protective effect of the natural product, chaetoglobosin K, on lindane- and dieldrin-induced changes in astroglia: identification of activated signaling pathways.

    Science.gov (United States)

    Sidorova, Tatyana S; Matesic, Diane F

    2008-06-01

    The purpose of the present study was to identify the biochemical mechanism(s) of the preventative and reversal effects of Chaetoglobosin K (ChK), a bioactive natural product, on inhibition of gap junction-mediated communication and connexin phosphorylation by the tumor promoting organochlorine compounds, lindane, and dieldrin. A fluorescent dye transfer assay was used to quantify gap junction-mediated communication and sensitivity to lindane and dieldrin. Analyses of connexin 43, PKC, ERK, GSK-3beta, Raf, and Akt kinase phosphorylation were performed by Western blotting. Pre-incubation of astroglial cells with 10 microM ChK prevented inhibition of dye transfer by lindane and dieldrin, which correlates with stabilization of the connexin 43 P2 isoform, and addition of ChK after lindane or dieldrin reversed the inhibitory effect, which correlated with re-appearance of the P2 isoform. Using phosphorylation site-specific antibodies, we demonstrated that lindane, dieldrin, and ChK all activated p44/42 ERK, but only ChK activated Akt kinase. ChK also activated a downstream effector of Akt, GSK-3beta, and activation of both kinases was inhibited by Wortmannin. Wortmannin also blocked ChK's ability to prevent dieldrin-induced inhibition of gap junction-mediated communication between RG-2 cells. ChK's protective effects, both preventative and reversal, on lindane and dieldrin inhibition of gap junction-mediated communication are associated with stabilization and reappearance of the connexin 43 P2 phosphoform and may be mediated by the Akt pathway.

  12. Estrogenic Activity of Coumestrol, DDT, and TCDD in Human Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kenneth Ndebele

    2010-05-01

    Full Text Available Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens. Using human cervical cancer cells (HeLa cells as a model, the effects of representative xenoestrogens (Coumestrol-a phytoestrogen, tetrachlorodioxin (TCDD-a herbicide and DDT-a pesticide on proliferation, cell cycle, and apoptosis were examined. These xenoestrogens and estrogen inhibited the proliferation of Hela cells in a dose dependent manner from 20 to 120 nM suggesting, that 17-β-estrtadiol and xenoestrogens induced cytotoxic effects. Coumestrol produced accumulation of HeLa cells in G2/M phase, and subsequently induced apoptosis. Similar effects were observed in estrogen treated cells. These changes were associated with suppressed bcl-2 protein and augmented Cyclins A and D proteins. DDT and TCDD exposure did not induce apoptosis. These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer.

  13. The PERK-eIF2α signaling pathway is involved in TCDD-induced ER stress in PC12 cells.

    Science.gov (United States)

    Duan, Zhiqing; Zhao, Jianya; Fan, Xikang; Tang, Cuiying; Liang, Lingwei; Nie, Xiaoke; Liu, Jiao; Wu, Qiyun; Xu, Guangfei

    2014-09-01

    Studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces apoptotic cell death in neuronal cells. However, whether this is the result of endoplasmic reticulum (ER) stress-mediated apoptosis remains unknown. In this study, we determined whether ER stress plays a role in the TCDD-induced apoptosis of pheochromocytoma (PC12) cells and primary neurons. PC12 cells were exposed to different TCDD concentrations (1, 10, 100, 200, or 500nM) for varying lengths of time (1, 3, 6, 12, or 24h). TCDD concentrations much higher than 10nM (100, 200, or 500nM) markedly increased glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) levels, which are hallmarks of ER stress. We also evaluated the effects of TCDD on ER morphology in PC12 cells and primary neurons that were treated with different TCDD concentrations (1, 10, 50, or 200nM) for 24h. Ultrastructural ER alterations were observed with transmission electron microscopy in PC12 cells and primary neurons treated with high concentrations of TCDD. Furthermore, TCDD-induced ER stress significantly promoted the activation of the PKR-like ER kinase (PERK), a sensor for the unfolded protein response (UPR), and its downstream target eukaryotic translation initiation factor 2 α (eIF2α); in contrast, TCDD did not appear to affect inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6), two other UPR sensors. Importantly, TCDD significantly inhibited eIF2α phosphorylation and triggered apoptosis in PC12 cells after 6-24h of treatment. Salubrinal, which activates the PERK-eIF2α pathway, significantly enhanced eIF2α phosphorylation in PC12 cells and attenuated the TCDD-induced cell death. In contrast, knocking down eIF2α using small interfering RNA markedly enhanced TCDD-induced cell death. Together, these results indicate that the PERK-eIF2α pathway plays an important role in TCDD-induced ER stress and apoptosis in PC12 cells.

  14. Adrenocorticotropin (ACTH) and corticosterone secretion by perifused pituitary and adrenal glands from rodents exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Pitt, J A; Buckalew, A R; House, D E; Abbott, B D

    2000-10-26

    Although in utero maternal stress has been shown to have lasting effects on rodent offspring, fetal effects of chemically-induced alterations of the maternal hypothalamic-pituitary-adrenal axis (HPA) have not been well studied. This study examined the effects of in vivo 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on pituitary-adrenal function in the male rat, pregnant female rat and pregnant female mouse. The secretion of adrenocorticotropin (ACTH) and corticosterone (CORT) in pituitary and adrenal glands, respectively, was assessed in ex vivo perifusion cultures. Male and pregnant female (gestation day 8) Sprague-Dawley rats were gavaged once with 10 microgram/kg TCDD, pregnant female mice once with 24 microgram/kg TCDD, and euthanized 10 days later. Hemi-pituitary (rat) or whole anterior pituitaries (mice) and right adrenal glands from the same animal were quartered, perifused under baseline and stimulated conditions. In both males and pregnant females, TCDD did not affect corticotropin releasing hormone (CRH)-stimulated ACTH secretion. Neither total pituitary ACTH nor plasma ACTH was altered in either sex or species by TCDD treatment. ACTH-stimulated CORT secretion was not affected by TCDD in either sex or species, and adrenal tissue and plasma CORT levels were unchanged in males and pregnant females by TCDD. However, the plasma ACTH:CORT ratio was decreased about 46% in male rats treated with TCDD. Plasma CORT levels were 23-fold higher and plasma ACTH levels were 1.5-fold higher in pregnant females than in male rats. In male versus female rats, adrenal CORT and anterior pituitary ACTH tissue levels were about 7.5- and 1.75-fold higher and ACTH, respectively. Female mouse adrenal tissue CORT was about 4-fold greater than female rat. The reduced plasma ACTH:CORT ratio in the male rat suggests that TCDD disturbs HPA function. Exposure of male rat to a 5-fold higher dose in earlier studies clearly demonstrated effects of TCDD on male rat HPA. The present

  15. Plasma Cytokine Concentrations in Workers Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    NARCIS (Netherlands)

    Saberi Hosnijeh, F.; Boers, D.; Portengen, L.; Bueno-de-Mesquita, H.B.; Heederik, D.; Vermeulen, R.

    2012-01-01

    Objectives: Few epidemiological studies have studied the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on blood cytokine levels. In this study we investigated changes in plasma levels of a large panel of cytokines, chemokines, and growth factors among workers from a Dutch historical cohort oc

  16. Handler, bystander and reentry exposure to TCDD from application of Agent Orange by C-123 aircraft during the Vietnam War.

    Science.gov (United States)

    Ross, John H; Hewitt, Andrew; Armitage, James; Solomon, Keith; Watkins, Deborah K; Ginevan, Michael E

    2015-02-01

    Using validated models and methods routinely employed by pesticide regulatory agencies, the absorbed dosages of Agent Orange (AO) herbicide contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were estimated for mixer/loaders, applicators, and individuals in the vicinity of applications of AO by C-123 aircraft during the Vietnam War. Resulting dosages of TCDD were then transformed to estimates of adipose residues, and compared to population biomonitoring of known mixer/loaders and applicators as well as ground troops in Vietnam and civilians in the U.S. Results demonstrate that mixer/loaders and applicators had the greatest exposures and their measured residues of TCDD in adipose were consistent with the estimated exposures. Further, the potentially exposed ground troops, including those who could have been directly sprayed during aerial defoliation, had measured adipose residues that were consistent with those in civilian U.S. populations with no defined source of exposure exposures and both of those cohorts had orders of magnitude less exposure than the mixer/loaders or applicators. Despite the availability of validated exposure modeling methods for decades, the quantitative TCDD dose estimates presented here are the first of their kind for the Vietnam conflict.

  17. Percutaneous Absorption of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) From Soil (Journal Article)

    Science.gov (United States)

    Eight dermal absorption (two in vivo; six in vitro) and one intravenous experiment were conducted using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either neat (high dose at ~250 µg/cm2 and low dose at 10 ng/cm2) or sorbed on a low organic (LOS) or high organic (HOS) soil at 1 ppm...

  18. Serum metabolomic pertubations among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    NARCIS (Netherlands)

    Hosnijeh, Fatemeh Saberi; Pechlivanis, Alexandros; Keun, Hector C.; Portengen, Lutzen; Bueno-de-Mesquita, H. Bas; Heederik, Dick; Vermeulen, Roel

    2013-01-01

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with multiple health effects. Mechanistic studies using metabolomics could provide supporting evidence for such associations by identifying relevant biological pathways. In this study, we investigated metabolic perturbations

  19. Changes in lymphocyte subsets in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    NARCIS (Netherlands)

    Saberi Hosnijeh, F.; Lenters, V.C.; Boers, D.; Portengen, L.; Baeten, E.; Bueno de Mesquita, H.B.; Heederik, D.J.J.; Bloem, A.C.; Vermeulen, R.C.H.

    2012-01-01

    OBJECTIVES: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to have toxic effects on the haematopoietic system in animals but epidemiological studies in humans have shown inconsistent results. In this cross-sectional study we investigated changes in peripheral blood cell counts and lymphocyte su

  20. The calculation of human toxicity thresholds of 2,3,7,8-TCDD; A Physiologically Based Pharmacokinetic modeling approach

    NARCIS (Netherlands)

    Zeilmaker MJ; van Eijkeren JCH; LBO

    1998-01-01

    Dit rapport beschrijft de toepassing van een 'Physiologically Based PharmacoKinetic' model (PBPK model) bij het berekenen van de verwachte 'No Adverse Effect Level' van 2,3,7,8-TetraChloroDibenzo-p-Dioxine (TCDD) bij de mens. Het model houdt rekening met variabiliteit en onzeker

  1. TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD

    Science.gov (United States)

    TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD. V M Richardson', J T Hamm2, and L S Birnbaum1. 'USEPA, ORD/NHEERL/ETD, Research Triangle Park, NC, USA, 'Curriculum in Toxicology, University of North Carolina, ...

  2. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces microglial nitric oxide production and subsequent rat primary cortical neuron apoptosis through p38/JNK MAPK pathway.

    Science.gov (United States)

    Li, Yuanye; Chen, Gang; Zhao, Jianya; Nie, Xiaoke; Wan, Chunhua; Liu, Jiao; Duan, Zhiqing; Xu, Guangfei

    2013-10-04

    It has been widely accepted that microglia, which are the innate immune cells in the brain, upon activation can cause neuronal damage. In the present study, we investigated the role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in regulating microglial nitric oxide production and its role in causing neuronal damage. The study revealed that TCDD stimulates the expression of inducible nitric oxide synthase (iNOS) as well as the production of nitric oxide (NO) in a dose- and time-dependent manner. Further, a rapid activation of p38 and JNK MAPKs was found in HAPI microglia following TCDD treatment. Blockage of p38 and JNK kinases with their specific inhibitors, SB202190 and SP600125, significantly reduced TCDD-induced iNOS expression and NO production. In addition, it was demonstrated through treating rat primary cortical neurons with media conditioned with TCDD treated microglia that microglial iNOS activation mediates neuronal apoptosis. Lastly, it was also found that p38 and JNK MAPK inhibitors could attenuate the apoptosis of rat cortical neurons upon exposure to medium conditioned by TCDD-treated HAPI microglial cells. Based on these observations, we highlight that the p38/JNK MAPK pathways play an important role in TCDD-induced iNOS activation in rat HAPI microglia and in the subsequent induction of apoptosis in primary cortical neurons.

  3. Comparative assessment of the global fate of α- and β-hexachlorocyclohexane before and after phase-out.

    Science.gov (United States)

    Wöhrnschimmel, Henry; Tay, Pascal; von Waldow, Harald; Hung, Hayley; Li, Yi-Fan; Macleod, Matthew; Hungerbuhler, Konrad

    2012-02-21

    Technical hexachlorocyclohexane (HCH) was one of the most widely used pesticides during the 20th century. Although production and use were phased-out during the 1990s, two of its major components, α- and β-HCH, are still ubiquitous in the environment. Here, we have collected and analyzed data on concentrations of α- and β-HCH in the atmosphere and oceans, including spatial and temporal trends and seasonalities. We apply a global fate and transport model to both isomers over the period 1950 to 2050 to rationalize current levels and trends at remote locations with estimated emissions and to forecast into the near future. Our model results indicate that secondary emissions from soils and oceans are currently controlling the observed rates of decline in the atmosphere. β-HCH is declining more slowly than α-HCH due to its higher persistence, and we hypothesize that it will eventually become the predominant isomer of HCH in the environment. The model reproduces over 70% of measured concentrations of α-HCH in air and ocean water within factors of 3 and 5, respectively, and over 70% of measured concentrations of β-HCH within factors of 8 and 20, respectively. The model results are only weakly sensitive to climate change-induced trends in Arctic sea-ice cover and temperature.

  4. A GIS model-based assessment of the environmental distribution of {gamma}-hexachlorocyclohexane in European soils and waters

    Energy Technology Data Exchange (ETDEWEB)

    Vizcaino, P., E-mail: pvizcaino@ecohidraulica.co [EC, DG JRC, Institute for Environment and Sustainability, Ispra (Italy); Pistocchi, A. [EC, DG JRC, Institute for Environment and Sustainability, Ispra (Italy)

    2010-10-15

    The MAPPE GIS based multimedia model is used to produce a quantitative description of the behaviour of {gamma}-hexachlorocyclohexane ({gamma}-HCH) in Europe, with emphasis on continental surface waters. The model is found to reasonably reproduce {gamma}-HCH distributions and variations along the years in atmosphere and soil; for continental surface waters, concentrations were reasonably well predicted for year 1995, when lindane was still used in agriculture, while for 2005, assuming severe restrictions in use, yields to substantial underestimation. Much better results were yielded when same mode of release as in 1995 was considered, supporting the conjecture that for {gamma}-HCH, emission data rather that model structure and parameterization can be responsible for wrong estimation of concentrations. Future research should be directed to improve the quality of emission data. Joint interpretation of monitoring and modelling results, highlights that lindane emissions in Europe, despite the marked decreasing trend, persist beyond the provisions of existing legislation. - An spatially-explicit multimedia modelling strategy was applied to describe the historical distribution of {gamma}-HCH in European soils and surface waters.

  5. Phytoremediation of hexachlorocyclohexane (HCH)-contaminated soils using Cytisus striatus and bacterial inoculants in soils with distinct organic matter content.

    Science.gov (United States)

    Becerra-Castro, Cristina; Kidd, Petra S; Rodríguez-Garrido, Beatriz; Monterroso, Carmela; Santos-Ucha, Paula; Prieto-Fernández, Angeles

    2013-07-01

    The performance of Cytisus striatus in association with different microbial inoculant treatments on the dissipation of the insecticide hexachlorocyclohexane (HCH) was studied. Two soils with different organic matter (A and B soil) content were spiked with 0 or 65 mg HCH kg(-1). Plants were either not inoculated (NI), or inoculated with the endophyte Rhodococcus erythropolis ET54b and the HCH-degrader Sphingomonas sp. D4 separately or in combination (ET, D4 and ETD4). Unplanted pots were also established. HCH phytotoxicity was more pronounced in the B soil. Soil HCH concentrations in unplanted pots were similar to initial concentrations, whereas concentrations were reduced after plant growth: by 20% and 8% in A and B soil, respectively. Microbial inoculants also modified HCH dissipation, although effects were soil-dependent. Inoculation with the combination of strains (ETD4) led to a significant enhancement in HCH dissipation: up to 53% in the A soil and 43% in the B soil.

  6. Biodegradation of dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) with plant and nutrients and their effects on the microbial ecological kinetics.

    Science.gov (United States)

    Sun, Guangdong; Zhang, Xu; Hu, Qing; Zhang, Heqing; Zhang, Dayi; Li, Guanghe

    2015-02-01

    Four pilot-scale test mesocosms were conducted for the remediation of organochlorine pesticides (OCPs)-contaminated aged soil. The results indicate that the effects on degradation of hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs) were in the following order: nutrients/plant bioaugmentation (81.18 % for HCHs; 85.4 % for DDTs) > nutrients bioaugmentation > plant bioaugmentation > only adding water > control, and nutrients/plant bioaugmentation greatly enhanced the degradation of HCHs (81.18 %) and DDTs (85.4 %). The bacterial community structure, diversity and composition were assessed by 454-pyrosequencing of 16S recombinant RNA (rRNA), whereas the abundance of linA gene was determined by quantitative polymerase chain reaction. Distinct differences in bacterial community composition, structure, and diversity were a function of remediation procedure. Predictability of HCH/DDT degradation in soils was also investigated. A positive correlation between linA gene abundance and the removal ratio of HCHs was indicated by correlation analyses. A similar relationship was also confirmed between the degradation of HCHs/DDTs and the abundance of some assemblages (Gammaproteobacteria and Flavobacteria). Our results offer microbial ecological insight into the degradation of HCHs and DDTs in aged contaminated soil, which is helpful for the intensification of bioremediation through modifying plant-microbe patterns, and cessation of costly and time-consuming assays.

  7. Kinetic and sequence-structure-function analysis of known LinA variants with different hexachlorocyclohexane isomers.

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    Pooja Sharma

    Full Text Available BACKGROUND: Here we report specific activities of all seven naturally occurring LinA variants towards three different isomers, α, γ and δ, of a priority persistent pollutant, hexachlorocyclohexane (HCH. Sequence-structure-function differences contributing to the differences in their stereospecificity for α-, γ-, and δ-HCH and enantiospecificity for (+- and (--α -HCH are also discussed. METHODOLOGY/PRINCIPAL FINDINGS: Enzyme kinetic studies were performed with purified LinA variants. Models of LinA2(B90A A110T, A111C, A110T/A111C and LinA1(B90A were constructed using the FoldX computer algorithm. Turnover rates (min(-1 showed that the LinAs exhibited differential substrate affinity amongst the four HCH isomers tested. α-HCH was found to be the most preferred substrate by all LinA's, followed by the γ and then δ isomer. CONCLUSIONS/SIGNIFICANCE: The kinetic observations suggest that LinA-γ1-7 is the best variant for developing an enzyme-based bioremediation technology for HCH. The majority of the sequence variation in the various linA genes that have been isolated is not neutral, but alters the enantio- and stereoselectivity of the encoded proteins.

  8. Polychlorinated biphenyls and hexachlorocyclohexanes in sediments and fish species from the Napoleon Gulf of Lake Victoria, Uganda.

    Science.gov (United States)

    Ssebugere, Patrick; Sillanpää, Mika; Kiremire, Bernard T; Kasozi, Gabriel N; Wang, Pu; Sojinu, Samuel O; Otieno, Peter O; Zhu, Nali; Zhu, Chaofei; Zhang, Haidong; Shang, Hongtao; Ren, Daiwei; Li, Yingming; Zhang, Qinghua; Jiang, Guibin

    2014-05-15

    Polychlorinated biphenyls (PCBs) and hexachlorocyclohexanes (HCHs) were analyzed in surface sediments (Napoleon Gulf on the northern shore of Lake Victoria. The analysis was done using a gas chromatograph (GC) coupled to a high resolution mass spectrometer for PCBs and a GC equipped with an electron capture detector for HCHs. Total (Σ) PCBs in the muscles of fish varied widely with mean values ranging from 41 to 670 pg g(-1) lipid weight (lw). The PCB levels in L. niloticus were significantly greater than those in O. niloticus. The large variability observed in the data was attributed to differences in feeding habits and trophic levels. While O. niloticus is a filter-eating fish species feeding mainly on phytoplankton and zooplankton, L. niloticus have predatory feeding behaviors and prefer a diet of live fish and, therefore, are more prone to bio-accumulate contaminants. The mean PCB concentrations in the sediments varied from 362 to 848 pg g(-1) dry weight. Variations in PCB levels were observed from one study site to another, this was attributed to the nature and particle size of the sediments. HCH isomers were detected in fish at mean concentrations of up to 45,900 pg g(-1) lw. The PCB and HCH concentrations were lower than those from previous studies elsewhere in literature and were below the maximum residue limits set by the European Commission and FAO/WHO Codex Alimentarius Commission, implying that the fish was fit for human consumption.

  9. Up- and down-regulation of beta-adrenoreceptors in rat cerebral cortex following exposure to isomers of hexachlorocyclohexane

    Energy Technology Data Exchange (ETDEWEB)

    Stark, L.; Hollinger, M.; Joy, R.

    1986-03-01

    The authors have shown that the gamma (lindane) and beta isomers of hexachlorocyclohexane (HCH) have opposite effects on the kindling model of epilepsy (gamma facilitates, beta retards kindling acquisition). In the present study the authors determined the effects of these two isomers on ..beta..-adrenoreceptors in rat brain using /sup 3/H-dihydroalprenolol as the ligand following 10 days treatment with 10 mg/kg p.o. of isomers or corn oil. Results showed a statistically significant decrease in the number of ..beta..-adrenoreceptors in cortical tissue taken from lindane treated rats. In contrast, there was a significant increase in the number of ..beta..-adreno receptors in cortical tissue taken from beta-HCH treated rats. Neither treatment caused a significant change in Kd. It is concluded that the ..beta..-adrenoreceptor system in rat brain is differentially affected by the isomers of HCH. Since the kindling model of epilepsy is sensitive to modulation in adrenergic function, this system may be involved in the pro- and anticonvulsant effects of these HCH isomers on kindling acquisition.

  10. Photocatalytic remediation of γ-hexachlorocyclohexane contaminated soils using TiO2 and montmorillonite composite photocatalyst

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xu; QUAN Xie; CHEN Shuo; ZHAO Hui-min; LIU Yu

    2007-01-01

    TiO2 and montmorillonite composite photocatalysts were prepared and applied in degrading γ-hexachlorocyclohexane(γ-HCH)in soils.After being spiked with γ-HCH,soil samples loaded with the composite photocatalysts were exposed to UV-light irradiation.The results indicated that the photocatalytic activities of the composite photocatalysts varied with the content of TiO2 in the order of 10%<70%<50%<30%.Moreover,the photocatalytic activity of the composite photocatalysts with TiO2 content 30% was higher than that of the pure P25 with the same mass of TiO2.The strong adsorption capacity of the composite photocatalysts and quantum size effect may contribute to its increased photocatalytic activities.In addition,effect of dosage of composite photocatalysts and soil pH on γ-HCH photodegradation was investigated. Pentachlorocyclohexene,trichlorocyclohexene,and dichlorobenzene were detected as photodegradation intermediates,which were gradually degraded with tlle phOtOdegradation evolution.

  11. ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR.

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    Wu, Yanming; Chen, Xiao; Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

    2014-01-01

    Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

  12. In utero exposure to TCDD alters Wnt signaling during mouse prostate development: linking ventral prostate agenesis to downregulated β-catenin signaling.

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    Schneider, Andrew J; Moore, Robert W; Branam, Amanda M; Abler, Lisa L; Keil, Kimberly P; Mehta, Vatsal; Vezina, Chad M; Peterson, Richard E

    2014-09-01

    In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes ventral prostate agenesis in C57BL/6J mice by preventing ventral prostatic budding in the embryonic urogenital sinus (UGS). TCDD (5 μg/kg, po) administered to pregnant dams on embryonic day 15.5 (E15.5) activates the aryl hydrocarbon receptor in the UGS mesenchyme, disrupting the mesenchymally derived paracrine signaling that instructs epithelial prostatic budding. How TCDD alters the mesenchymal milieu is not well understood. We previously showed that TCDD disrupts some aspects of Wnt signaling in UGSs grown in vitro. Here we provide the first comprehensive, in vivo characterization of Wnt signaling in male E16.5 UGSs during normal development, and after in utero TCDD exposure. Vehicle- and TCDD-exposed UGSs were probed by in situ hybridization to assess relative abundance and localization of RNA from 46 genes that regulate Wnt signaling. TCDD altered the staining pattern of five genes, increasing staining for Wnt10a and Wnt16 and decreasing staining for Ror2, Rspo2, and Wif1. We also used immunohistochemistry to show, for the first time, activation of β-catenin (CTNNB1) signaling in ventral basal epithelium of control UGSs at E16.5. This onset of CTNNB1 signaling occurred immediately prior to the initiation of ventral prostatic budding and is characterized by a pronounced increase in CTNNB1 nuclear localization and subsequent expression of the CTNNB1 signaling target gene, Lef1. In utero TCDD exposure prevented the onset of CTNNB1 signaling and LEF1 expression in the ventral basal epithelium, thereby elucidating a likely mechanism by which TCDD contributes to failed prostatic budding in the ventral UGS.

  13. Modeling the dynamic changes in concentrations of {gamma}-hexachlorocyclohexane ({gamma}-HCH) in Tianjin region from 1953 to 2020

    Energy Technology Data Exchange (ETDEWEB)

    Tao, S. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China) and Department of Geosciences, University of Missouri, Kansas City, MO 64110-2499 (United States)]. E-mail: taos@urban.pku.edu.cn; Yang, Y. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Cao, H.Y. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Liu, W.X. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Coveney, R.M. [Department of Geosciences, University of Missouri, Kansas City, MO 64110-2499 (United States); Xu, F.L. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Cao, J. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Li, B.G. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Wang, X.J. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Hu, J.Y. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China); Fang, J.Y. [Laboratory for Earth Surface Processes, College of Environmental Sciences, Peking University, Beijing 100871 (China)

    2006-01-15

    A level IV fugacity model was used to simulate the dynamic changes of {gamma}-hexachlorocyclohexane ({gamma}-HCH) concentrations in environmental media in Tianjin, China. A similar model (level III) was previously used and validated under steady state conditions; this paper explores its dynamic behavior. Application of the level IV fugacity model has been validated using independently observed {gamma}-HCH concentrations in various media during the early 1980s and during 2001. Sensitivity analysis was conducted using coefficient-of-variation normalized sensitivity coefficients. The model was also subject to uncertainty analysis using Monte Carlo simulation. It was found that concentrations of {gamma}-HCH reached within 95% of their steady-state levels in all media after less than 15 years. Around one order-of-magnitude decreases in {gamma}-HCH concentrations in various media occurred between 1993 and 2001. We project that {gamma}-HCH concentrations will decrease another 1.7-1.9 orders of magnitude to reach 1.1 (0.9-1.2)x10{sup -14}, 2.7 (2.5-3.0)x10{sup -1}, 1.2 (1.1-1.3)x10{sup -7}, and 6.1 (5.4-6.8)x10{sup -8} mol/m{sup 3}, in air, water, soil, and sediment, respectively, by 2020. The sensitivities and true uncertainty of the model are discussed. -- Levels of lindane in various media of Tianjin area decreased significantly during the last decade and will drop more than one order of magnitude in the next 20 years.

  14. [Beta-hexachlorocyclohexane contamination in dairy farms of the Sacco River Valley, Latium, Italy, 2005. A retrospective cohort study].

    Science.gov (United States)

    Sala, Marcello; Caminiti, Antonino; Rombolà, Pasquale; Volpe, Aldo; Roffi, Cristina; Caperna, Osvaldo; Miceli, Maria; Ubaldi, Alessandro; Battisti, Antonio; Scaramozzino, Paola

    2012-01-01

    in March 2005, the Italian National Monitoring System on Chemical Residuals in Food of Animal Origin detected levels of the pesticide beta-hexachlorocyclohexane (ß-HCH) that were 20 times higher than the legal limit of 0.003 mg/kg in bulk milk from a dairy farm in the Sacco River valley. ß-HCH, a lindane isomer and possible human carcinogen, was subsequently found in milk from several neighboring farms. A study was therefore undertaken to evaluate the extent and risk factors for contamination. all dairy cattle farms in the valley were enrolled in a retrospective cohort study and their bulk milk analyzed for ß-HCH. A questionnaire was administered to farmers to evaluate possible exposure factors. cases: dairy farms with at least one result indicating ß-HCH ≥ 0.002 mg/kg in bulk milk during the period april-june 2005; exposure: feeding animals on fodder cultivated in soils watered with and/or flooded by river water; participants: IZSLT, RMG Local Health Unit, FR Local Health Unit. attack rate, relative risk, attributable proportion among exposed. of 244 farms tested, 34 met the case definition (attack rate 14%). The exposure to fodder cultivated in soils watered with and/or flooded by river water was observed in 33/34 (97%) case-farms and in 23/210 (10.9%) of those with contamination milk (RR 110.8; 95%CI 15.5- 792). Attributable proportion among exposed was more than 99%. fodder cultivated near a contaminated river was the main risk factor for ß-HCH contaminated milk. On the basis of the epidemiologic evidence and laboratory testing, watering local fields with river water and production of fodder in farms with contaminated soil was banned, and all the animals from positive farms were culled.

  15. Genomic organization and genomic structural rearrangements of Sphingobium japonicum UT26, an archetypal γ-hexachlorocyclohexane-degrading bacterium.

    Science.gov (United States)

    Nagata, Yuji; Natsui, Shunsuke; Endo, Ryo; Ohtsubo, Yoshiyuki; Ichikawa, Natsuko; Ankai, Akiho; Oguchi, Akio; Fukui, Shigehiro; Fujita, Nobuyuki; Tsuda, Masataka

    2011-12-10

    The complete genome sequencing of a γ-hexachlorocyclohexane-degrading strain, Sphingobium japonicum UT26, revealed that the genome consists of two circular chromosomes [with sizes of 3.5 Mb (Chr1) and 682kb (Chr2)], a 191-kb large plasmid (pCHQ1), and two small plasmids with sizes of 32 and 5kb. The lin genes are dispersed on Chr1, Chr2, and pCHQ1. Comparison of the UT26 genome with those of other sphingomonad strains demonstrated that the "specific"lin genes for conversion of γ-HCH to β-ketoadipate (linA, linB, linC, linRED, and linF) are located on the DNA regions unique to the UT26 genome, suggesting the acquisition of these lin genes by horizontal transfer events. On the other hand, linGHIJ and linKLMN are located on the regions conserved in the genomes of sphingomonads, suggesting that the linGHIJ-encoded β-ketoadipate pathway and the LinKLMN-type ABC transporter system are involved in core functions of sphingomonads. Based on these results, we propose a hypothesis that UT26 was created by recruiting the specific lin genes into a strain having core functions of sphingomonads. Most of the specific lin genes in UT26 are associated with IS6100. Our analysis of spontaneous linA-, linC-, and linRED-deletion mutants of UT26 revealed the involvement of IS6100 in their deduced genome rearrangements. These facts strongly suggest that IS6100 plays important roles both in the dissemination of the specific lin genes and in the genome rearrangements.

  16. A spatial, statistical approach to map the risk of milk contamination by β-hexachlorocyclohexane in dairy farms

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    Sabrina Battisti

    2013-11-01

    Full Text Available In May 2005, beta-hexachlorocyclohexane (β-HCH was found in a sample of bovine bulk milk from a farm in the Sacco River valley (Latium region, central Italy. The primary source of contamination was suspected to be industrial discharge into the environment with the Sacco River as the main mean of dispersion. Since then, a surveillance programme on bulk milk of the local farms was carried out by the veterinary services. In order to estimate the spatial probability of β- HCH contamination of milk produced in the Sacco River valley and draw probability maps of contamination, probability maps of β-HCH values in milk were estimated by indicator kriging (IK, a geo-statistical estimator, and traditional logistic regression (LR combined with a geographical information systems approach. The former technique produces a spatial view of probabilities above a specific threshold at non-sampled locations on the basis of observed values in the area, while LR gives the probabilities in specific locations on the basis of certain environmental predictors, namely the distance from the river, the distance from the pollution site, the elevation above the river level and the intrinsic vulnerability of hydro-geological formations. Based on the β-HCH data from 2005 in the Sacco River valley, the two techniques resulted in similar maps of high risk of milk contamination. However, unlike the IK method, the LR model was capable of estimating coefficients that could be used in case of future pollution episodes. The approach presented produces probability maps and define highrisk areas already in the early stages of an emergency before sampling operations have been carried out.

  17. Human health risk from hexachlorocyclohexane and dichlorodiphenyltrichloroethane pesticides, through consumption of vegetables: estimation of daily intake and hazard quotients

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    Bhupander Kumar

    2013-08-01

    Full Text Available People are encouraged to consume more fresh vegetables due to the high nutritional value and fibre contents in vegetables. At the same time, due to pesticidal residue in vegetables, vegetable consumption is considered as an important route of pesticides uptake by human beings. Pesticides, particularly organochlorines such as Aldrin, heptachlor and isomers of dichlorodiphe - nyltrichloroethane (DDT and hexachlorocyclohexane (HCH are a major concern because of their persistence, bioaccumulation, toxicity, and long-range environmental transport ability. Hence information on such toxic contaminants in vegetables is very essential, due to human health concern. In order to assess the potential health risks associated with vegetable consumption due to pesticidal residues of DDT and HCH, sixty four samples of commonly available vegetables were collected from a local market in West Bengal, India and analysed for DDT and HCH. In this study, estimated average daily intake of HCHs and DDTs through vegetables was ranged between 5.0x10–8–9.1x10–6 mg kg–1 day–1 with an average value of 2.0x10–6 mg kg–1 day–1. Human health risk was assessed in terms of incremental lifetime cancer risk and health hazard index was between 1.7x10–8–8.8x10–6 and 1.5x10–7– 1.7x10–2, respectively. Generated results were compared with maximum residual levels and reference values, were within acceptable limits and suggested no health risk to the human populations. Therefore, an extensive study on vegetables with the inclusion of other persistent organic pollutants and toxic metals should be carried out to know the overall scenario of contamination of vegetables.

  18. The impact of chlordane and dieldrin contamination of well water on cancer rates in North Stamford, Connecticut.

    Science.gov (United States)

    Lo, Ana M M L; Tsai, Wei-Yann; Lo, K M Steve

    2011-10-01

    High levels of the carcinogenic organochlorine pesticides chlordane and dieldrin have been reported in the well water of homes in North Stamford. It is unclear if the contamination is associated with an increase in the cancer rate in North Stamford. We reviewed the demographics of the towns surrounding North Stamford and chose New Canaan, Wilton, Weston, and Darien as towns with sufficiently similar demographics that would permit comparison of cancer incidence with North Stamford. Data were obtained from the Connecticut Tumor Registry regarding the number of different cancers diagnosed per year from 1998 to 2007 in North Stamford and the four nearby towns. We compared the annual cancer incidence of these communities in total and by cancer types. There was no statistically significant difference in the average annual cancer incidence from 1998 to 2007 between North Stamford and the four other communities. There was also no statistically significant difference seen in the incidence of the various cancer types. Chlordane and dieldrin contamination of the well water of homes in North Stamford may not be associated with a higher incidence of cancer.

  19. Gender differences in transcriptional signature of developing rat testes and ovaries following embryonic exposure to 2,3,7,8-TCDD.

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    Solange Magre

    Full Text Available Dioxins are persistent organic pollutants interfering with endocrine systems and causing reproductive and developmental disorders. The objective of our project was to determine the impact of an in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD on reproductive function of male and female offspring in the rat with a special emphasis on the immature period. We used a low dose of TCDD (unique exposure by oral gavage of 200 ng/kg at 15.5 days of gestation in order to mirror a response to an environmental dose of TCDD not altering fertility of the progeny. We choose a global gene expression approach using Affymetrix microarray analysis, and testes of 5 days and ovaries of 14 days of age. Less than 1% of the expressed genes in gonads were altered following embryonic TCDD exposure; specifically, 113 genes in ovaries and 56 in testes with 7 genes common to both sex gonads. It included the repressor of the aryl hydrocarbon receptor (Ahrr, the chemokines Ccl5 and Cxcl4 previously shown to be regulated by dioxin in testis, Pgds2/Hpgds and 3 others uncharacterized. To validate and extend the microarray data we realized real-time PCR on gonads at various developmental periods of interest (from 3 to 25 days for ovaries, from 5 to the adult age for testes. Overall, our results evidenced that both sex gonads responded differently to TCDD exposure. For example, we observed induction of the canonic battery of TCDD-induced genes coding enzymes of the detoxifying machinery in ovaries aged of 3-14 days of age (except Cyp1a1 induced at 3-10 days but not in testes of 5 days (except Ahrr. We also illustrated that inflammatory pathway is one pathway activated by TCDD in gonads. Finally, we identified several new genes targeted by TCDD including Fgf13 in testis and one gene, Ptgds2/Hpgds regulated in the two sex gonads.

  20. 2,3,7,8-TCDD-mediated toxicity in peripheral blood mononuclear cells is alleviated by the antioxidants present in Gelidiella acerosa: an in vitro study.

    Science.gov (United States)

    Kalaiselvan, Ilavarasi; Senthamarai, Muthumanikandan; Kasi, Pandima Devi

    2016-03-01

    Seaweeds have been used as a source of traditional medicine worldwide for the treatment of various ailments, mainly due to their ability to quench the free radicals. The present study aims at evaluating the protective effect of methanolic extract of Gelidiella acerosa, an edible red seaweed against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced toxicity in peripheral blood mononuclear cells (PBMC). For evaluating the protective effect of G. acerosa, PBMC were divided into four groups: vehicle control, TCDD (10 nM), TCDD + G. acerosa (300 μg/ml), and G. acerosa alone treated. Scavenging of intracellular reactive oxygen species (ROS) induced by TCDD was assessed by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Alterations at macromolecular level were quantified through lipid peroxidation (LPO) level, protein carbonyl content (PCC) level, and comet assay. The cellular morphology upon TCDD toxicity and G. acerosa treatment was obtained by light microscopy and histopathological studies. The chemical composition present in the methanolic extract of G. acerosa was determined by gas chromatography-mass spectrometry (GC-MS) analysis. The results reveal that 10 nM TCDD caused significant (P TCDD treatment resulted in a significant increase in the production of ROS, LPO (114 ± 0.09), and PCC (15.13 ± 1.53) compared to the control, whereas co-treatment with G. acerosa significantly (P TCDD-induced genotoxicity and cell damage. GC-MS analysis showed the presence of n-hexadecanoic acid (retention time (RT) 13.15), cholesterol (RT 28.80), α-D-glucopyranose, 4-O-α-D-galactopyranosyl (RT 20.01), and azulene (RT 4.20). The findings suggest that G. acerosa has a strong protective ability against TCDD-induced cytotoxicity, oxidative stress, and DNA damage.

  1. Toxicity induced by dieldrin and chlorpyrifos in the freshwater crayfish Cambarellus montezumae (Cambaridae

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    Sandra Díaz-Barriga Arceo

    2015-03-01

    Full Text Available The toxicity induced by insecticides in aquatic organisms is of utmost relevance because it may give a clue about the degree of health or damage of the involved ecosystem. In the present report, we determined the effect of dieldrin (DD and chlorpyrifos (CP on the freshwater crayfish, Cambarellus montezumae. The organisms (4-6cm in diameter were collected in the Ignacio Ramírez Reservoir, situated at 50km Northeast of Mexico City, in the Rio Lerma Basin. Initially, we determined the LC50 value with the Probit method, then the DNA damage with single cell gel electrophoresis (comet assay applied at 24, 48, and 72h of exposure to the brain and hepatopancreas of animals exposed (in reconstituted water to 0.05 and 0.5µg/L of each insecticide. In the hepatopancreas of the same organisms, we determined the lipid peroxidation by applying the TBARS test. DNA damage and lipid peroxidation were also evaluated with the same methods to organisms exposed in water from the reservoir. In regard to the LC50 at 72h of exposure, we found a value of 5.1µg/L and a value of 5.62µg/L for DD and CP, respectively. The comet assay applied at different exposure times showed significant DNA damage to both organs, with respect to the control level. In the case of DD, statistical significance was observed for the two doses in the whole evaluated schedule. CP was genotoxic in the brain with the high dose at 72h, and in the hepatopancreas with the two tested doses at all evaluated exposure times. Also, a significant lipid peroxidation increase was detected with the two doses of insecticides. In the study with water from the reservoir, a more pronounced DNA damage was detected. Our results showed strong DNA damage induced by both insecticides in the crayfish, as well as a correlation with the lipid peroxidation effect, suggesting that oxidative stress is involved in the genotoxic alteration. Our results also showed the usefulness of the studied organism as well as the

  2. Toxicity induced by dieldrin and chlorpyrifos in the freshwater crayfish Cambarellus montezumae (Cambaridae).

    Science.gov (United States)

    Díaz, Sandra; Arceo, Barriga; Martínez-Tabche, Laura; Alvarez-González, Isela; López López, Eugenia; Madrigal-Bujaidar, Eduardo

    2015-03-01

    The toxicity induced by insecticides in aquatic organisms is of utmost relevance because it may give a clue about the degree of health or damage of the involved ecosystem. In the present report, we determined the effect of dieldrin (DD) and chlorpyrifos (CP) on the freshwater crayfish, Cambarellus montezumae. The organisms (4-6 cm in diameter) were collected in the Ignacio Ramirez Reservoir, situated at 50 km Northeast of Mexico City, in the Rio Lerma Basin. Initially, we determined the LC50 value with the Probit method, then the DNA damage with single cell gel electrophoresis (comet assay applied at 24, 48, and 72 h of exposure) to the brain and hepatopancreas of animals exposed (in reconstituted water) to 0.05 and 0.5 microg/L of each insecticide. In the hepatopancreas of the same organisms, we determined the lipid peroxidation by applying the TBARS test. DNA damage and lipid peroxidation were also evaluated with the same methods to organisms exposed in water from the reservoir. In regard to the LC50, at 72 h of exposure, we found a value of 5.1 microg/L and a value of 5.62 microg/L for DD and CP, respectively. The comet assay applied at different exposure times showed significant DNA damage to both organs, with respect to the control level. In the case of DD, statistical significance was observed for the two doses in the whole evaluated schedule. CP was genotoxic in the brain with the high dose at 72 h, and in the hepatopancreas with the two tested doses at all evaluated exposure times. Also, a significant lipid peroxidation increase was detected with the two doses of insecticides. In the study with water from the reservoir, a more pronounced DNA damage was detected. Our results showed strong DNA damage induced by both insecticides in the crayfish, as well as a correlation with the lipid peroxidation effect, suggesting that oxidative stress is involved in the genotoxic alteration. Our results also showed the usefulness of the studied organism as well as the

  3. Combined 17β-Estradiol with TCDD Promotes M2 Polarization of Macrophages in the Endometriotic Milieu with Aid of the Interaction between Endometrial Stromal Cells and Macrophages.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available The goal of this study is to elucidate the effects of 17β-estradiol and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin on macrophage phenotypes in the endometriotic milieu. Co-culture of endometrial stromal cells (ESCs and U937 cells (macrophage cell line was performed to simulate the endometriotic milieu and to determine the effects of 17β-estradiol and/or TCDD on IL10, IL12 production and HLA-DR, CD86 expression by U937 macrophages. We found that combining 17β-estradiol with TCDD has a synergistic effect on inducing M2 activation when macrophages are co-cultured with ESCs. Moreover, the combination of 17β-estradiol and TCDD significantly enhanced STAT3 and P38 phosphorylation in macrophages. Differentiation of M2 macrophages induced by 17β-estradiol and TCDD were effectively abrogated by STAT3 and P38MAPK inhibitors, but not by ERK1/2 and JNK inhibitors. In conclusion, 17β-estradiol and TCDD in the ectopic milieu may lead to the development of endometriosis by inducing M2 polarization of macrophages through activation of the STAT3 and P38MAPK pathways.

  4. Combined 17β-Estradiol with TCDD Promotes M2 Polarization of Macrophages in the Endometriotic Milieu with Aid of the Interaction between Endometrial Stromal Cells and Macrophages.

    Science.gov (United States)

    Wang, Yun; Chen, Hong; Wang, NingLing; Guo, HaiYan; Fu, Yonglun; Xue, Songguo; Ai, Ai; Lyu, Qifeng; Kuang, Yanping

    2015-01-01

    The goal of this study is to elucidate the effects of 17β-estradiol and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on macrophage phenotypes in the endometriotic milieu. Co-culture of endometrial stromal cells (ESCs) and U937 cells (macrophage cell line) was performed to simulate the endometriotic milieu and to determine the effects of 17β-estradiol and/or TCDD on IL10, IL12 production and HLA-DR, CD86 expression by U937 macrophages. We found that combining 17β-estradiol with TCDD has a synergistic effect on inducing M2 activation when macrophages are co-cultured with ESCs. Moreover, the combination of 17β-estradiol and TCDD significantly enhanced STAT3 and P38 phosphorylation in macrophages. Differentiation of M2 macrophages induced by 17β-estradiol and TCDD were effectively abrogated by STAT3 and P38MAPK inhibitors, but not by ERK1/2 and JNK inhibitors. In conclusion, 17β-estradiol and TCDD in the ectopic milieu may lead to the development of endometriosis by inducing M2 polarization of macrophages through activation of the STAT3 and P38MAPK pathways.

  5. Activation of neuronal nitric oxide synthase (nNOS) signaling pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced neurotoxicity.

    Science.gov (United States)

    Jiang, Junkang; Duan, Zhiqing; Nie, Xiaoke; Xi, Hanqing; Li, Aihong; Guo, Aisong; Wu, Qiyun; Jiang, Shengyang; Zhao, Jianya; Chen, Gang

    2014-07-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been reported to cause alterations in cognitive and motor behavior during both development and adulthood. In this study, the neuronal nitric oxide synthase (nNOS) signaling pathway was investigated in differentiated pheochromocytoma (PC12) cells to better understand the mechanisms of TCDD-induced neurotoxicity. TCDD exposure induced a time- and dose-dependent increase in nNOS expression. High levels of nitric oxide (NO) production by nNOS activation induced mitochondrial cytochrome c (Cyt-c) release and down-regulation of Bcl-2. Additionally, TCDD increased the expression of active caspase-3 and significantly led to apoptosis in PC12 cells. However, these effects above could be effectively inhibited by the addition of 7-nitroindazole (7-NI), a highly selective nNOS inhibitor. Moreover, in the brain cortex of Sprague-Dawley (SD) rats, nNOS was also found to have certain relationship with TCDD-induced neuronal apoptosis. Together, our findings establish a role for nNOS as an enhancer of TCDD-induced apoptosis in PC12 cells.

  6. Effects of selected food phytochemicals in reducing the toxic actions of TCDD and p,p'-DDT in U937 macrophages.

    Science.gov (United States)

    Sciullo, Eric M; Vogel, Christoph F; Wu, Dalei; Murakami, Akira; Ohigashi, Hajime; Matsumura, Fumio

    2010-12-01

    To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p'-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT-PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells. We tested auraptene on DDT-induced reactive oxygen species (ROS) formation in U937 macrophages and found that auraptene is a powerful agent antagonizing this action of DDT. To confirm the significance of these actions of zerumbone and auraptene at the cellular level, we assessed their influence on TCDD-induced apoptosis resistance in intact U937 macrophages and found that they are capable of reversing this action of TCDD. In conclusion, zerumbone and auraptene were identified to be the most effective agents in protecting U937 macrophages from developing these cell toxic effects of TCDD and DDT.

  7. RNA-sequencing analysis of TCDD-induced responses in zebrafish liver reveals high relatedness to in vivo mammalian models and conserved biological pathways.

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Li

    Full Text Available TCDD is one of the most persistent environmental toxicants in biological systems and its effect through aryl hydrocarbon receptor (AhR has been well characterized. However, the information on TCDD-induced toxicity in other molecular pathways is rather limited. To fully understand molecular toxicity of TCDD in an in vivo animal model, adult zebrafish were exposed to TCDD at 10 nM for 96 h and the livers were sampled for RNA-sequencing based transcriptomic profiling. A total of 1,058 differently expressed genes were identified based on fold-change>2 and TPM (transcripts per million >10. Among the top 20 up-regulated genes, 10 novel responsive genes were identified and verified by RT-qPCR analysis on independent samples. Transcriptomic analysis indicated several deregulated pathways associated with cell cycle, endocrine disruptors, signal transduction and immune systems. Comparative analyses of TCDD-induced transcriptomic changes between fish and mammalian models revealed that proteomic pathway is consistently up-regulated while calcium signaling pathway and several immune-related pathways are generally down-regulated. Finally, our study also suggested that zebrafish model showed greater similarity to in vivo mammalian models than in vitro models. Our study indicated that the zebrafish is a valuable in vivo model in toxicogenomic analyses for understanding molecular toxicity of environmental toxicants relevant to human health. The expression profiles associated with TCDD could be useful for monitoring environmental dioxin and dioxin-like contamination.

  8. Inhibition of CK2 Activity by TCDD via Binding to ATP-competitive Binding Site of Catalytic Subunit:Insight from Computational Studies

    Institute of Scientific and Technical Information of China (English)

    XU Xian-jin; CANNISTRARO Salvatore; BIZZARRI Anna-rita; ZENG Yi; CHEN Wei-zu; WANG Cun-xin

    2013-01-01

    Alternative mechanisms of toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD),instead of the binding to aryl hydrocarbon receptor(AhR),have been taken into consideration.It has been recently shown that TCDD reduces rapidly the activity of CK2(casein kinase Ⅱ) both in vivo and in vitro.It is found that TCDD has high molecular similarities to the known inhibitors of CK2 catalytic subunit(CK2α).This suggests that TCDD could also be an ATP-competitive inhibitor of CK2α.In this work,docking TCDD to CK2 was carried out based on the two structures of CK2α from maize and human,respectively.The binding free energies of the predicted CK2α-TCDD complexes estimated by the molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method are from -85.1 kJ/mol to-114.3 kJ/mol for maize and are from-96.1 kJ/mol to-118.2 kJ/mol for human,which are comparable to those estimated for the known inhibitor and also ATP with CK2α.The energetic analysis also reveals that the van der Waals interaction is the dominant contribution to the binding free energy.These results are also useful for designing new drugs for a target of overexpressing CK2 in cancers.

  9. Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes.

    Science.gov (United States)

    Kerkvliet, Nancy I; Steppan, Linda B; Vorachek, William; Oda, Shannon; Farrer, David; Wong, Carmen P; Pham, Duy; Mourich, Dan V

    2009-07-01

    The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), is a novel inducer of adaptive Tregs. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent AHR ligand, induces adaptive CD4+CD25+ Tregs during an acute graft-versus-host (GvH) response and prevents the generation of allospecific cytotoxic T lymphocytes. TCDD also suppresses the induction of experimental autoimmune encephalitis in association with an expanded population of Foxp3+ Tregs. In this study, we show that chronic treatment of NOD mice with TCDD potently suppresses the development of autoimmune Type 1 diabetes in parallel with greatly reduced pancreatic islet insulitis and an expanded population of CD4+CD25+Foxp3+ cells in the pancreatic lymph nodes. When treatment with TCDD was terminated after 15 weeks (23 weeks of age), mice developed diabetes over the next 8 weeks in association with lower numbers of Tregs and decreased activation of AHR. Analysis of the expression levels of several genes associated with inflammation, T-cell activation and/or Treg function in pancreatic lymph node cells failed to reveal any differences associated with TCDD treatment. Taken together, the data suggest that AHR activation by TCDD-like ligands may represent a novel avenue for treatment of immune-mediated diseases.

  10. TCDD-induced transcriptional profiles in different mouse strains that have an identical AhR genotype

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qing; Suzuki, Junko S.; Tohyama, Chiharu; Ohsako, Seiichiroh [Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Tsukuba (Japan); Takei, Teiji [Environmental Health and Safety Division, Ministry of the Environment, Kasumigaseki, Tokyo (Japan); Lin, Tinmin; Peterson, R.E. [Wisconsin Univ., Wisconsin, MA (United States). School of Pharmacy and Molecular and Environmental Toxicology Center

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that is known to cause hepatotoxicity, teratogenicity and carcinogenicity. A characteristic feature in the toxicity of TCDD is exceptionally large differences in susceptibility among animal species or even strains belonging to the same species. These strain differences in susceptibility to TCDD have now been elucidated to be due to the difference in ligand binding affinity or transcriptional activity of the aryl hydrocarbon receptor (AhR). Actually the C57BL/6 type AhR (AhR{sup b}) showed 6-fold higher ligand binding affinity than the DBA/2 type AhR (AhR{sup d}). The H/W rat AhR has a C-terminal truncation of the transactivating domain compared to the L-E rat AhR. On the other hand, there is considerable species variability in response sensitivity to TCDD that cannot be ascribed simply to polymorphisms of the AhR gene. A non-AhR gene susceptibility loci for hepatic porphyria has been observed in mice treated with iron compounds prior to TCDD injection by using a quantitative trait locus analysis of an F2 intercross between susceptible C57BL/6 and resistant DBA/2 stains. In the rat, a gene B with Han/Wistar type AhR is likely to be involved in resistance to TCDD lethality. These observations suggest that other modulating genes, so-called ''modifier genes'', have profound effects on the AhR-mediated gene expression phenotype. Based on the nucleotide sequence of the AhR coding region, the BALB/c, CBA/J, and C3H/He mouse strains are clustered together on a single branch. In the present study, we try to confirm the existence of modifiers by using microarray analysis to examine hepatic gene expression after TCDD exposure in BALB/c, CBA/J, and C3H/He mice. To recognize the existence of a modifier besides the AhR, it is a prerequisite experimental condition that the analyzed strains have an identical AhR genotype. Therefore, we selected BALB/c, CBA/J, and C3H/He mice as the model

  11. Ethoxyresorufin-O-deethylase (EROD) induction by TCDD, PeCDF and PCB 126 in bobwhite quail hepatocytes.

    Science.gov (United States)

    Jones, Stephanie P; Farmahin, Reza; Kennedy, Sean W

    2014-07-01

    World Health Organization (WHO) toxic equivalency factors are used to calculate toxic equivalent (TEQ) concentrations of complex mixtures of dioxin-like compounds (DLCs), such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls (PCBs), for mammals, fish and birds. The TEQ concept assumes that all species of a taxa respond with similar sensitivity to individual DLCs, but several reports do not support this assumption for birds. Our laboratory is conducting research to attempt to uncover the fundamental mechanism(s) underlying the reasons why avian species differ in sensitivity to DLCs. The present study determined concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on ethoxyresorufin-O-deethylase (EROD) activity in primary cultures of northern bobwhite quail (Colinus virginianus) hepatocytes. Bobwhite quail were studied because (1) this species is used in the laboratory for toxicity testing and (2) the amino acids at all locations within the ligand binding domain (LBD) of aryl hydrocarbon receptor 1 (AHR1) in bobwhite quail and ring necked pheasant (Phasianus colchicus) are identical. Because earlier work indicated the importance of the identity of amino acids at key sites within the AHR1 LBD, we hypothesized that bobwhite quail and ring necked pheasant hepatocytes should have similar sensitivity to EROD induction by DLCs. ECthreshold-based relative sensitivity of the bobwhite quail compared to chicken for TCDD, PeCDF and PCB 126 was 0.11, 0.17 and 0.02, respectively. The rank order of potency was PeCDF > TCDD > PCB 126. The results confirm that bobwhite quail and ring-necked pheasant hepatocytes have similar sensitivity to EROD induction by TCDD, PeCDF and PCB 126.

  12. Coumestrol, Bisphenol-A, DDT, and TCDD Modulation of Interleukin-2 Expression in Activated CD+4 Jurkat T Cells

    Directory of Open Access Journals (Sweden)

    Robert W. McMurray

    2004-02-01

    Full Text Available Endogenous estrogens are known to modulate several components of immune response, including interleukin-2 (IL-2 production. IL-2 is a cytokine that plays an important role in adaptive immune responses. These responses may be modulated by xenoestrogens such as coumestrol, bisphenol A (BPA, DDT, and TCDD. In this research, we examined the effects and potential mechanisms of action of these estrogenic compounds on IL-2 production in activated CD4+ Jurkat T cells. IL-2 production was analyzed by ELISA and Western Blot. At the transcriptional level, protein expression was examined by RT-PCR. Coumestrol, DDT and TCDD (but not BPA significantly suppressed IL-2 production in activated CD4+ Jurkat T cells, at the transcriptional and translational levels. The transcriptional suppression of IL-2 was associated with decreased protein levels of NF-κβ, an important IL-2 positive transcription factor, without affecting the expression of Iκ−Βα protein expression, an important inhibitor of NF-κβ nuclear translocation. Although the direct mechanisms of xenoestrogens modulation of the immune system remain to be elucidated, coumestrol-, DDT- and TCDD-induced suppression of IL-2 may have ramifications for our understanding of the impact of xenoestrogens on health and disease.

  13. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases bilirubin formation but hampers quantitative hepatic conversion of biliverdin to bilirubin in rats with wild-type AH receptor.

    Science.gov (United States)

    Niittynen, Marjo; Simanainen, Ulla; Pohjanvirta, Raimo; Sankari, Satu; Tuomisto, Jouni T

    2014-06-01

    In haem degradation, haem oxygenase-1 (HO-1) first cleaves haem to biliverdin, which is reduced to bilirubin by biliverdin IXα reductase (BVR-A). The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin in moderately TCDD-resistant line B (Kuopio) rats. Using line B and two TCDD-sensitive rat strains, the present study set out to probe the dose-response and biochemical mechanisms of this accumulation. At 28 days after exposure to 3-300 μg/kg TCDD in line B rats, already the lowest dose of TCDD tested, 3 μg/kg, affected serum bilirubin conjugates, and after doses ≥100 μg/kg, the liver content of bilirubin, biliverdin and their conjugates (collectively 'bile pigments') as well as HO-1 was elevated. BVR-A activity and serum bile acids were increased only by the doses of 100 and 300 μg/kg TCDD, respectively. Biliverdin conjugates correlated best with biliverdin suggesting it to be their immediate precursor. TCDD (100 μg/kg, 10 days) increased hepatic bilirubin and biliverdin levels also in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. Hepatic bilirubin and bile acids, but not biliverdin, were increased in feed-restricted L-E control rats. In TCDD-sensitive line C (Kuopio) rats, 10 μg/kg of TCDD increased the body-weight-normalized biliary excretion of bilirubin. Altogether, the results suggest that at acutely toxic doses, TCDD induces the formation of bilirubin in rats. However, concurrently, TCDD seems to hamper the quantitative conversion of biliverdin to bilirubin in line B and L-E rats' liver. Biliverdin conjugates are most likely formed as secondary products of biliverdin.

  14. Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: kinetics and trials to enhance elimination in two patients

    Energy Technology Data Exchange (ETDEWEB)

    Geusau, A. [Dept. of Dermatology, Univ. of Vienna, Vienna (Austria); Schmaldienst, S.; Derfler, K. [Dept. of Internal Medicine, Univ. of Vienna, Vienna (Austria); Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany); Abraham, K. [Dept. of Pediatric Pneumology and Immunology, Children' s Hospital, Charite, Humboldt Univ., Berlin (Germany)

    2002-06-01

    In spring 1998, two women were diagnosed with severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication. Over the following 3 years, TCDD levels were monitored under various attempts to enhance its elimination, and the half-lives were evaluated. Olestra, a non-digestible, non-absorbable dietary fat substitute, was continuously administered to the patients either as pure substance or in potato-chips. Additionally, in the more severely contaminated patient, we studied whether low-density lipoprotein (LDL)-apheresis, an extracorporeal means of blood lipid elimination, was effective in reducing the TCDD body burden. The blood concentrations initially measured in spring 1998 were 144,000 pg/g blood fat in patient 1 and 26,000 pg/g in patient 2, the highest levels ever measured in adults. In March 2001, concentrations in blood fat were 35,900 and 9,500 pg/g, corresponding to overall elimination half-lives of 560 days (1.5 years) in patient 1 and 1050 days (2.9 years) in patient 2, which are considerably shorter than median values of 7-9 years reported for background and moderate exposure levels. Calculations of the TCDD half-lives and measurements of TCDD elimination via different routes allowed the calculation of an unidentified route of elimination, representing 78 and 62% of the overall elimination in patient 1 and 2, respectively, probably due to an induced hepatic metabolism caused by the high TCDD exposure. As previously reported, administration of olestra was found to be effective in increasing the fecal excretion of TCDD. Due to the short half-lives in our patients, the effect of olestra on the overall elimination was relatively small, but is expected to be much greater for 'normal' half-lives. LDL-apheresis was shown to eliminate TCDD, corresponding to the eliminated blood fat. When employed twice a week, the amount of TCDD excreted by this method was comparable to fecal excretion. In view of costs and time involved, LDL-apheresis does not seem to

  15. Oral administration of hesperidin, a citrus flavonone, in rats counteracts the oxidative stress, the inflammatory cytokine production, and the hepatotoxicity induced by the ingestion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Bentli, Recep; Ciftci, Osman; Cetin, Asli; Unlu, Merve; Basak, Nese; Cay, Mahmut

    2013-06-01

    The objective of the current study was to investigate the protective effects of hesperidin against oxidative stress, altered cytokines levels and histological changes in rats induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into four equal groups (Control, TCDD, hesperidin and TCDD+hesperidin). TCDD and hesperidin were given by gavage, dissolved in corn oil at doses of 2 μ/kg/week and 50 mg/kg/day respectively. The blood and tissue samples were taken from all rats on the 60(th) day, to be analyzed for the determination of oxidative stress, histological changes and cytokine levels. The results indicated that hesperidin prevented oxidative damage caused by TCDD via decrease lipid peroxidation and increased antioxidant defense systems. It also reversed the histological damage induced by TCDD. Although, TCDD led to a significant increase in TNF-α and IL-1β levels, hesperidin treatment was able to normalize these values in rats. In conclusion, it was shown that TCDD caused adverse effects as regards cytokine levels, histological alterations and oxidative stress in rats. However, hesperidin treatment mitigated these toxic effects. These results suggest that hesperidin could play a protective role against TCDD toxicity.

  16. Distribution pathways of hexachlorocyclohexane isomers in a soil-plant-air system. A case study with Cynara scolymus L. and Erica sp. plants grown in a contaminated site

    Energy Technology Data Exchange (ETDEWEB)

    Calvelo Pereira, R. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, Campus Sur, 15782 Santiago de Compostela (Spain)], E-mail: edrobert@usc.es; Monterroso, C.; Macias, F.; Camps-Arbestain, M. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, Campus Sur, 15782 Santiago de Compostela (Spain)

    2008-09-15

    This study focuses on the main routes of distribution and accumulation of different hexachlorocyclohexane (HCH) isomers (mainly {alpha}-, {beta}-, {gamma}- and {delta}-HCH) in a soil-plant-air system. A field assay was carried out with two plant species, Cynara scolymus L. and Erica sp., which were planted either: (i) directly in the HCH-contaminated soil; or (ii) in pots filled with uncontaminated soil, which were placed in the HCH-contaminated soil. Both plant species accumulated HCH in their tissues, with relatively higher accumulation in above-ground biomass than in roots. The {beta}-HCH isomer was the main isomer in all plant tissues. Adsorption of HCH by the roots from contaminated soil (soil {yields} root pathway) and adsorption through the aerial biomass from either the surrounding air, following volatilization of the contaminant (soil {yields} air {yields} shoot pathway), and/or contact with air-suspended particles contaminated with HCH (soil particles {yields} shoot pathway) were the main mechanisms of accumulation. These results may have important implications for the use of plants for reducing the transfer of contaminants via the atmosphere. - Hexachlorocyclohexane isomers are preferentially accumulated in above-ground tissues of plants grown in a heavily contaminated site.

  17. Immunohistochemical analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the developmental dentate gyrus and hippocampal fimbria in fetal mice.

    Science.gov (United States)

    Kobayashi, Yoshihiro; Hirano, Tetsushi; Omotehara, Takuya; Hashimoto, Rie; Umemura, Yuria; Yuasa, Hideto; Masuda, Natsumi; Kubota, Naoto; Minami, Kiichi; Yanai, Shogo; Ishihara-Sugano, Mitsuko; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2015-11-01

    Dioxins are widespread persistent environmental contaminants with adverse impacts on humans and experimental animals. Behavioral and cognitive functions are impaired by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. TCDD exerts its toxicity via the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The hippocampus, which plays important roles in episodic memory and spatial function, is considered vulnerable to TCDD-induced neurotoxicity, because it contains the AhR. We herein investigated the effects of TCDD toxicity on hippocampal development in embryonic mice. TCDD was administered to dams at 8.5 days postcoitum with a single dose of 20, 200, 2,000 and 5,000 ng/kg body weight (groups T20, T200, T2000 and T5000, respectively), and the brains were dissected from their pups at embryonic day 18.5. Immunohistochemical analysis demonstrated that the Glial Fibrillary Acidic Protein (GFAP) immunoreactivities in the dentate gyrus (DG) were reduced in the T5000 group. Granular GFAP immunoreactivity was observed in the hippocampal fimbria, and the number of immunoreactive fimbria was significantly decreased in the T5000 group. The number of Proliferating Cell Nuclear Antigen (PCNA)-positive cells was decreased in all TCDD-exposed groups and significantly reduced in the T20, T200 and T5000 groups. Together, these results demonstrate that maternal TCDD exposure has adverse impacts on neural stem cells (NSCs), neural precursor cells (NPCs) and granular cells in the DG and disrupts the NSC maintenance and timing of differentiation in the hippocampal fimbria, which in turn interrupt neuronal development in future generations of mice.

  18. Three-generation experiment showed female C57BL/6J mice drink drainage canal water containing low level of TCDD-like activity causing high pup mortality.

    Science.gov (United States)

    Huang, Li; Huang, Ren; Ran, Xin-Ru; Liu, Han-Ying; Zhang, Yu; Dai, Li-Jun; Li, Bing

    2011-01-01

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs) and similar compounds are toxic to animals and humans. Based on a yeast reporter system, AhR-activating ligands similar in concentration to 2 ng/l of TCDD were detected in two canal waters in Guangzhou, China. In this study, a three-generation experiment was conducted to assess the reproductive and developmental risks associated with these waters in C57BL/6J female mice, including female reproduction, pup indices, reproductive hormone levels, and levels of AhR, ARNT, and CYP1A2 in the uterus. Similar reproductive toxic effects were produced in the offspring of mice that drank the canal water as would occur if they drank 2 ng/l/day TCDD. The major reproductive indices that were affected included mating time and gestation length over all the generations. A striking finding is the TCDD (2 ng/l) and the water samples significantly reduced Day 4 pup survival rates in the F2 and F3. Both TCDD exposure and drinking canal water decreased estradiol-17β (E2) levels in the multiparous females and decreased follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 levels in the virgin females. Immunochemical staining revealed that the AhR and CYP1A2 positive signals were enhanced, and the ARNT positive signal was weakened in the uteri of mice drinking water with TCDD (2 ng/l) and the canal water samples. These results imply that the canal water contains AhR ligands that could induce similar toxic effects as do low levels of TCDD. Exposure to these contaminants can significantly impair the reproductive health of female mice. Considering this canals are open directly to Pearl River, whether these effects could be caused in human reproduction and development warrants further study.

  19. Superantigen-primed T cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) replicate poorly following recall encounter

    Energy Technology Data Exchange (ETDEWEB)

    Faulconer, Laura; Camacho, Iris; Nagarkatti, Mitzi [Virginia Commonwealth University, Department of Microbiology and Immunology, Medical College of Virginia Campus, 980613, Richmond, VA (United States); Nagarkatti, Prakash S. [Virginia Commonwealth University, Department of Pharmacology and Toxicology, Medical College of Virginia Campus, 980613, Richmond, VA (United States)

    2006-03-15

    The current study investigated the effect of tetrachlorodibenzo-p-dioxin (TCDD) on the ability of staphylococcal enterotoxin A (SEA)-primed T cells to divide by dual-labeling the cells with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and antibodies against the specific T cell receptors. C57BL/6 wild-type mice were injected ip with TCDD (10 {mu}g/kg body weight) followed by hind footpad injections of SEA (10 {mu}g/footpad). The draining popliteal lymph nodes (PLN) were harvested 1-4 days posttreatment, labeled with CFSE and cultured for 1-4 days without further stimulation or in the presence of the recall antigen. TCDD-exposed SEA-reactive V{beta}3+ and V{beta}11+ T cells showed decreased cell divisions upon in vitro culture in the absence of any stimulation, which correlated with increased levels of apoptosis. The recall cell-division response was also defective in SEA-reactive T cells isolated from TCDD-exposed mice. However, during the recall response, cells from TCDD-exposed mice did not exhibit a defect in apoptosis, suggesting the defective recall response may result from a state of anergy rather than increased apoptosis. Using AhR knockout (KO) mice, we found AhR involvement in the regulation of defective cell division and apoptosis induced by TCDD. Together, these data demonstrate, while TCDD-induced apoptosis may account for the decreased primary T cell proliferative response, that the reduced cell division seen during subsequent exposure to recall antigen may result from a state of anergy. The study also demonstrates that a combined use of superantigen and CFSE may offer a simple and useful tool to monitor the ability of immunotoxicants to alter the proliferative responsiveness of antigen-specific T cells. (orig.)

  20. Dioxin (TCDD induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    Directory of Open Access Journals (Sweden)

    Mohan Manikkam

    Full Text Available Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  1. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    Science.gov (United States)

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  2. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) blocks ovulation by a direct action on the ovary without alteration of ovarian steroidogenesis: lack of a direct effect on ovarian granulosa and thecal-interstitial cell steroidogenesis in vitro.

    Science.gov (United States)

    Son, D S; Ushinohama, K; Gao, X; Taylor, C C; Roby, K F; Rozman, K K; Terranova, P F

    1999-01-01

    The main purpose of this study was to investigate the direct effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on ovarian function including ovulation and steroidogenesis. In vivo effects of TCDD were investigated on ovulation and alteration of circulating and ovarian steroid hormones in immature hypophysectomized rats (IHR) primed with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). In addition, in vitro effects of TCDD on the steroidogenesis of granulosa cells (GC), theca-interstitial cells (TIC), and whole ovarian dispersates derived from the ovary of IHR were investigated. In the ovulation model, rats were hypophysectomized on Day 23 of age. On Day 26, the IHR were given 20 microg TCDD/kg by gavage. The next day eCG (10 IU) was injected sc to stimulate follicular development. Fifty-two hours after eCG, 10 IU hCG was given to induce ovulation. TCDD (20 microg/kg) blocked ovulation and reduced ovarian weight in IHR. Concentrations of progesterone (P4), androstenedione (A4), and estradiol (E2) in sera and ovaries were not altered by TCDD at 12, 24, 48, and 72 h after eCG. except for a two-fold increase in ovarian concentration of A4 at 48 h after TCDD. However, this higher concentration of A4 at 48 h after TCDD did not reflect that of A4 in sera and did not correlate with E2 in either sera or ovaries. In isolated GC from untreated IHR, TCDD (0.1 to 100 nM) had no significant effect on P4 and E2 after stimulation by LH or FSH. In TIC and whole ovarian dispersates containing GC, TIC, and other ovarian cells, TCDD (0.1 to 800 nM) had no effect on A4 and P4 secretion stimulated by LH. Using RT-PCR, AhR mRNA was shown to be expressed constitutively in the whole ovary of IHR with maximum down-regulation at 6 h after TCDD (20 microg/kg). Ovarian CYP1A1 was induced maximally at 6 h after TCDD, whereas CYP1B1 could not be detected. The induction of AhR related genes by TCDD in the ovary implies the existence of AhR-mediated signal

  3. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces Fas-dependent activation-induced cell death in superantigen-primed T cells

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    Camacho, Iris A.; Nagarkatti, Mitzi [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Prakash S. [Department of Pharmacology and Toxicology, PO Box 980613, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2002-10-01

    Immune response against a foreign antigen is characterized by a growth phase, in which antigen-specific T cells clonally expand, followed by a decline phase in which the activated T cells undergo apoptosis, a process termed activation-induced cell death (AICD). In the current study, we have investigated the phase at which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acts to downregulate the antigen-specific T cell response. To this end, C57BL/6 +/+ mice were injected with staphylococcal enterotoxin A (SEA) into the footpads (10 {mu}g/footpad), and simultaneously treated with TCDD (10 or 50 {mu}g/kg intraperitoneally). At various time points, the draining lymph node (LN) cells were analyzed for SEA-activated T cells. The data demonstrated that in C57BL/6 +/+ mice, TCDD treatment did not alter the growth phase but facilitated the decline phase of SEA-reactive T cells. TCDD caused a significant decrease in the percentage and absolute numbers of CD4{sup +} and CD8{sup +} SEA-responsive T cells expressing V{beta}3{sup +} and V{beta}11{sup +} but did not affect SEA-nonresponsive V{beta}8{sup +} T cells. Upon in vitro culture, TCDD-exposed SEA-immunized LN cells exhibited increased levels of apoptosis when compared with the vehicle controls. When Fas-deficient (C57BL/6 lpr/lpr) or Fas ligand defective (C57BL/6 gld/gld) mice were treated with TCDD, they failed to exhibit a decrease in percentage and cellularity of SEA-reactive T cells, thereby suggesting a role of Fas-Fas ligand interactions in the TCDD-induced downregulation of SEA-reactive T cell response. The resistance to TCDD-induced decrease in T cell responsiveness to SEA seen in Fas- and FasL-mutant mice was neither due to decreased aryl hydrocabon receptor (AhR) expression nor to altered T cell responsiveness to SEA. The current study demonstrates that TCDD does not prevent T cell activation, but prematurely induces Fas-based AICD, which may contribute to the deletion of antigen-primed T cells. (orig.)

  4. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the endogenous metabolism of all-trans-retinoic acid in the rat

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    Schmidt, Carsten K.; Nau, Heinz [Department of Food Toxicology, School of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173, Hannover (Germany); Hoegberg, Pi; Fletcher, Nicholas; Nilsson, Charlotte B.; Trossvik, Christina; Haakansson, Helen [Institute of Environmental Medicine, Karolinska Institutet, 17177, Stockholm (Sweden)

    2003-07-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to influence vitamin A homeostasis. In order to investigate the mechanism behind this retinoid disruption, male Sprague-Dawley rats were exposed to TCDD at doses ranging from 0.1 to 100 {mu}g/kg body weight, and were killed 3 days after exposure. Additional groups of rats were killed 1 and 28 days after a single oral dose of 10 {mu}g TCDD/kg body weight. Serum, kidney, and liver were investigated for retinoid levels, as well as gene expression and enzyme activities relevant for retinoid metabolism. Besides the well known effects of TCDD on apolar retinoids, i.e. decreased hepatic and increased renal retinyl ester (RE) levels, we have found dose-dependent elevation of all-trans-retinoic acid (all-trans-RA) levels in all investigated tissues. In the liver, 9-cis-4-oxo-13,14-dihydro-RA was drastically decreased by TCDD in a dose-dependent manner. In serum, cis-isomers of all-trans-RA, including 9,13-di-cis-RA, were significantly reduced already at the lowest dose level. Protein and mRNA levels of cellular retinol binding protein I (CRBP-I) in liver or kidneys were not significantly altered by TCDD exposure at doses at which retinoid levels were affected, making CRBP-I an unlikely candidate to account for the alterations in retinoid metabolism caused by TCDD. The expression and activities of relevant cytochrome P450 (CYP) enzymes with potential roles in all-trans-RA synthesis and/or degradation (CYP1A1, 1A2, and 2B1/2) were also monitored. A possible role of CYP1A1 in TCDD-induced all-trans-RA synthesis is suggested from the time-course relationship between CYP1A1 activity and all-trans-RA levels in liver and kidney. The significant alteration of the all-trans-RA metabolism has the potential to contribute significantly to the toxicity of TCDD. (orig.)

  5. Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Chang, Yue; Feng, LiFang; Miao, Wei

    2011-07-01

    Dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are persistent in the environment and cause continuous toxic effects in humans and aquatic life. Tetrahymena thermophila has the potential for use as a model for research regarding toxicants. In this study, this organism was used to analyze a genome-wide microarray generated from cells exposed to DDT, TBT and TCDD. To accomplish this, genes differentially expressed when treated with each toxicant were identified, after which their functions were categorized using GO enrichment analysis. The results suggested that the responses of T. thermophila were similar to those of multicellular organisms. Additionally, the context likelihood of relatedness method (CLR) was applied to construct a TCDD-relevant network. The T-shaped network obtained could be functionally divided into two subnetworks. The general functions of both subnetworks were related to the epigenetic mechanism of TCDD. Based on analysis of the networks, a model of the TCDD effect on T. thermophila was inferred. Thus, Tetrahymena has the potential to be a good unicellular eukaryotic model for toxic mechanism research at the genome level.

  6. Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland.

    Science.gov (United States)

    Katarzyńska, Dorota; Hrabia, Anna; Kowalik, Kinga; Sechman, Andrzej

    2015-03-01

    The aim of this study was to compare the in vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) and 2,2'4,4',5,5'-hexachlorobiphenyl (PCB153; non-coplanar PCB) on mRNA expression of thyroid-restricted genes, i.e. sodium iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and thyroid hormone secretion from the thyroid gland of the laying chicken. Relative expression levels of NIS, TG and TPO genes and thyroxine (T4) and triiodothyronine (T3) secretion from the thyroidal explants were quantified by the real-time qPCR and RIA methods, respectively. In comparison with the control group, TCDD and PCB 126 significantly increased mRNA expression of TPO and TG genes. TCDD did not affect NIS mRNA levels, but PCB 126 decreased its expression. No effect of PCB 153 on the expression of these genes was observed. TCDD and PCB 126 significantly decreased T4 and T3 secretion. There was no significant effect of PCB 153 on these hormone secretions. In conclusion, the results obtained show that in comparison with non-coplanar PCB 153, TCDD and coplanar PCB 126 can directly affect thyroid hormone synthesis and secretion, and in consequence, they may disrupt the endocrine function of the thyroid gland of the laying chicken. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. [The Use of In-situ Biomonitoring to Assess the Fate and Effects of Sediment-associated Dieldrin in Lakes at the Rocky Mountain Arsenal : Drafts and Comments : 1993-1994

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    US Fish and Wildlife Service, Department of the Interior — This document consists of multiple drafts of the proposal 'The Use of In-situ Biomonitoring to Assess the Fate and Effects of Sediment-associated Dieldrin in Lakes...

  8. The adverse effects of aldrin and dieldrin on both myometrial contractions and the secretory functions of bovine ovaries and uterus in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wrobel, Michał H., E-mail: m.wrobel@pan.olsztyn.pl; Grzeszczyk, Marlena; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2015-05-15

    Aldrin and dieldrin are chloroorganic insecticides which are recognised as endocrine disruptors. The aim of the study was to investigate their effect on the secretory functions of the uterus and ovary and on myometrial contractions. Myometrial strips and uterine and ovarian cells from nonpregnant cows were incubated with the xenobiotics (0.1, 1 or 10 ng/ml) for 24 or 72 h. Next, their effect on viability of myometrial, endometrial, granulosa and luteal cells, myometrial strip contractions, the synthesis and secretion of prostaglandins (PGs: PGF2α and PGE2) from uterine cells, the secretion of oestradiol (E2), testosterone (T) and oxytocin (OT) from granulosa cells and the secretion of progesterone (P4) and OT from luteal cells were determined. Neither of the xenobiotics (10 ng/ml) affected (P > 0.05) the viability of the ovarian and uterine cells, while both (0.1–10 ng/ml) decreased (P < 0.05) the basal and OT-stimulated myometrial contractions. In spite of these effects, neither of the insecticides affected (P > 0.05) the synthesis and the secretion of PGs from the myometrial cells. Although they also did not impair the secretion of the PGs from the endometrial cells, they abolished (P < 0.05) the stimulatory effect of OT (P < 0.05) on the secretion of the PGs and stimulated (P < 0.05) the secretion of OT from the granulosa and luteal cells. Moreover, aldrin and dieldrin stimulated secretion of E2 and T from the granulosa cells, while only dieldrin increased (P < 0.05) the secretion of P4 from luteal cells. The data show that aldrin and dieldrin stimulated the secretory function of the cultured granulosa and luteal cells and inhibited the myometrial contractions of cows in vitro, which may affect on natural parturition. - Highlights: • Aldrin and dieldrin inhibited bovine myometrial contractions. • The studied xenobiotics stimulated steroids and oxytocin secretion from ovaries. • Prostaglandins are not involved in adverse effect of the xenobiotics on

  9. Promotion of breast cancer by β-Hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice

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    Matsumura Fumio

    2007-07-01

    Full Text Available Abstract Background Exposure to β-Hexachlorocyclohexane (β-HCH, a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. Previous studies in our laboratory have demonstrated the ability of β-HCH to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-Neu (= erbB2 or HER-2 expression and kinase activation in both the BG-1 and MCF-7 cell lines. In addition, long term exposure (33 passages to β-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype. Methods In this current study, we decided to investigate the long-term effects of β-HCH in both the MCF10AT1 cell line which was derived from a normal epithelial cell line by stably transfecting a mutated c-Ha-ras and a MMTV-Neu mouse model for mammary cancer in vivo. MCF10AT1 cells were exposed for 20 passages with β-HCH, 4-OH-Tamoxifen (Tam, or 17-β-estradiol (E2 after which cells were analyzed for proliferation rates and mRNA expression by RT-PCR. In our in vivo studies, MMTV-Neu mice were injected with β-HCH and observed for tumor formation over a 70 week period. Results β-HCH and Tam selected MCF10AT1 cells demonstrated increased mRNA expression of MMP-13 (collagenase-3 a marker of increased invasiveness. β-HCH treatment was also seen to increase the expression in a number of proto-oncogenes (c-Neu, Cyclin D1, p27, cell status markers (Met-1, CK19, and the inflammatory marker NFκB. Previous studies, have demonstrated the role of these markers as evidence of malignant transformations, and further illustrate the ability of β-HCH to be carcinogenic. To demonstrate β-HCH's tumorigenic properties in an in vivo system, we used an MMTV-Neu mouse model. MMTV-Neu is a c-Neu overexpressing strain which has been shown to spontaneously develop mammary tumors at later stages of aging. In this experiment,

  10. The Effect of Dose on 2,3,7,8-TCDD Tissue Distribution, Metabolism and Elimination in CYP1A2 (-/-) Knockout and C57BL/6N Parental Strains of Mice

    Science.gov (United States)

    Numerous metabolism studies have demonstrated that the highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is poorly metabolized. A hallmark feature of TCDD exposure is induction of hepatic CYP1A2 and subsequent sequestration leading to high liver to fat concentration ratios. This study was in...

  11. The effect of dose on 2,3,7,8-TCDD tissue distribution, metabolism and elimination in CYP1A2(-/_) knockout and C57BL/6N parental strains of mice

    Science.gov (United States)

    Numerous metabolism studies have demonstrated that the toxic contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is poorly metabolized. A hallmark feature of TCDD exposure is induction of hepatic CYP1A2 and subsequent sequestration leading to high liver-to-fat concentration ra...

  12. Serum concentrations of TCDD and other dioxin-like compounds in US Air Force veterans of Operation Ranch Hand.

    Science.gov (United States)

    Pavuk, Marian; Patterson, Donald G; Turner, Wayman E

    2014-05-01

    We measured serum concentrations of seven dibenzo-p-dioxin congeners (PCDDs), ten dibenzofurans (PCDFs), four non-ortho polychlorinated biphenyls (noPCBs) and six mono-ortho polychlorinated biphenyls (moPCBs) in 1950 veterans of the Vietnam War. The veterans were participants in the Air Force Health Study (AFHS) who attended the final medical examination in 2002. Blood samples were collected from 777 Ranch Hands involved in the aerial spraying of herbicides in Vietnam and a comparison group of 1173 veterans ("Comparisons") who served in Southeast Asia during the same time period. Results for moPCBs were based on a random subsample of 800 veterans. The median 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 2002 were 5.0 pg g(-1) lipid in Ranch Hands and 2.2 pg g(-1) lipid in Comparisons. No substantial differences were found in measured concentrations of other PCDDs, PCDFs, and noPCBs. Similarly, no substantial differences were found for moPCBs in the subsample. The median total dioxin toxic equivalent (TEQ) in Ranch Hands was 18.7 pg g(-1) lipid for PCDDs, 3.4 pg g(-1) lipid for PCDFs, and 3.2 pg g(-1) lipid for noPCBs. Median TEQs in Comparisons were 14.4 pg g(-1) lipid for PCDDs, 3.5 pg g(-1) lipid for PCDFs, and 3.3 pg g(-1) lipid for noPCBs. These TEQs, with the exception of PCDD TEQ in Ranch Hands (primarily due to elevated TCDD), were similar to or lower than those reported for similar age and gender groups in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). These findings support the assumption that the Ranch Hand veterans were not more highly exposed to dioxin-like compounds other than TCDD than were Comparison veterans or the general US population.

  13. TCDD-Induced Activation of Aryl Hydrocarbon Receptor Inhibits Th17 Polarization and Regulates Non-Eosinophilic Airway Inflammation in Asthma.

    Directory of Open Access Journals (Sweden)

    Xiao-ming Li

    Full Text Available The aryl hydrocarbon receptor (AhR, a transcription factor of the bHLH/PAS family, has recently been demonstrated to regulate T cell differentiation. Whether AhR activation participates in allergic airway inflammation remains unknown. In the current study, using a non-eosinophilic asthma model, we demonstrate that 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD, a potent AhR ligand, reduced the airway infiltration of neutrophils, airway hyperresponsiveness and Th17 cytokine expression. Furthermore, stimulation with TCDD promoted Treg differentiation and inhibited Th17 differentiation. However, the maturation of dendritic cells may not be inhibited by AhR activation. This study thus indicates a critical role of TCDD-induced AhR activation in the regulation of non-eosinophilic airway inflammation.

  14. Utilizing thin-film solid-phase extraction to assess the effect of organic carbon amendments on the bioavailability of DDT and dieldrin to earthworms.

    Science.gov (United States)

    Andrade, Natasha A; Centofanti, Tiziana; McConnell, Laura L; Hapeman, Cathleen J; Torrents, Alba; Nguyen, Anh; Beyer, W Nelson; Chaney, Rufus L; Novak, Jeffrey M; Anderson, Marya O; Cantrell, Keri B

    2014-02-01

    Improved approaches are needed to assess bioavailability of hydrophobic organic compounds in contaminated soils. Performance of thin-film solid-phase extraction (TF-SPE) using vials coated with ethylene vinyl acetate was compared to earthworm bioassay (Lumbricus terrestris). A DDT and dieldrin contaminated soil was amended with four organic carbon materials to assess the change in bioavailability. Addition of organic carbon significantly lowered bioavailability for all compounds except for 4,4'-DDT. Equilibrium concentrations of compounds in the polymer were correlated with uptake by earthworms after 48d exposure (R(2) = 0.97; p Dieldrin and DDX were respectively 18% and 11% less bioavailable in contaminated soil relative to spiked soil despite >40yr of aging. Results show that TF-SPE can be useful in examining potential risks associated with contaminated soils and to test effectiveness of remediation efforts. Published by Elsevier Ltd.

  15. Analysis of α,β,γ-hexachlorocyclohexanes in water by novel activated carbon fiber-solid phase microextraction coupled with gas chromatography--mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    SUN Tong-hua; FANG Neng-hu; ZHU Nan-wen; WANG Ya-lin; JIA Jin-ping

    2004-01-01

    A fast and simple method for determination of α, β, γ-hexachlorocyclohexanes (HCHs) in water using activated carbon fiber-solid phase microextraction(ACF-SPME) were pressented. Results showed the performance of adsorption and desorption of three HCHs on ACF were excellent. A wide linear range from 10 to 100 μg/L and detection limits of the ng/L level were obtained using ACF-SPME with GC-MS in selected ion monitoring(SIM) acquisition mode. The proposed method was also successfully applied for determination of three HCHs in tap water. Compared to commercial fibers, ACF showed some advantages such as better resistance to solvents, higher thermal stability, long lifetime and lower cost. The data demonstrated that GC-MS with ACF-SPME is well suitable for the analysis of HCHs in water.

  16. Comparison of TCDD-elicited genome-wide hepatic gene expression in Sprague-Dawley rats and C57BL/6 mice.

    Science.gov (United States)

    Nault, Rance; Kim, Suntae; Zacharewski, Timothy R

    2013-03-01

    Although the structure and function of the AhR are conserved, emerging evidence suggests that downstream effects are species-specific. In this study, rat hepatic gene expression data from the DrugMatrix database (National Toxicology Program) were compared to mouse hepatic whole-genome gene expression data following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For the DrugMatrix study, male Sprague-Dawley rats were gavaged daily with 20μg/kg TCDD for 1, 3 and 5days, while female C57BL/6 ovariectomized mice were examined 1, 3 and 7days after a single oral gavage of 30μg/kg TCDD. A total of 649 rat and 1386 mouse genes (|fold change|≥1.5, P1(t)≥0.99) were differentially expressed following treatment. HomoloGene identified 11,708 orthologs represented across the rat Affymetrix 230 2.0 GeneChip (12,310 total orthologs), and the mouse 4×44K v.1 Agilent oligonucleotide array (17,578 total orthologs). Comparative analysis found 563 and 922 orthologs differentially expressed in response to TCDD in the rat and mouse, respectively, with 70 responses associated with immune function and lipid metabolism in common to both. Moreover, QRTPCR analysis of Ceacam1, showed divergent expression (induced in rat; repressed in mouse) functionally consistent with TCDD-elicited hepatic steatosis in the mouse but not the rat. Functional analysis identified orthologs involved in nucleotide binding and acetyltransferase activity in rat, while mouse-specific responses were associated with steroid, phospholipid, fatty acid, and carbohydrate metabolism. These results provide further evidence that TCDD elicits species-specific regulation of distinct gene networks, and outlines considerations for future comparisons of publicly available microarray datasets.

  17. Environmental fate and dietary exposures of humans to TCDD as a result of the spraying of Agent Orange in upland forests of Vietnam.

    Science.gov (United States)

    Armitage, James M; Ginevan, Michael E; Hewitt, Andrew; Ross, John H; Watkins, Deborah K; Solomon, Keith R

    2015-02-15

    The fate and transport of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) released into the environment of South Vietnam (SVN) as a consequence of the aerial application of the herbicidal defoliant Agent Orange (AO) were simulated for a generic upland forest scenario and followed over a 50-year period (1965, 1968 and 1970 onwards). Modeled concentrations of TCDD in the environment were then used as inputs to a human exposure model, which focused on long-term exposures via the food chain. Intake rates and body burdens of TCDD were estimated for adult males over the course of the simulation period and compared to available biomonitoring data. One of the most important factors determining the magnitude of the simulated human exposure to TCDD was the fraction of the chemical deposited directly to soil (where it was assumed to have a degradation half-life of 10 or 15years) relative to the fraction assumed to remain on/in the forest canopy following the spray application (where it was assumed to have a degradation half-life of ≤48h). The simulated body burdens under the various scenarios considered were broadly consistent with the biomonitoring data from SVN collected in the mid-1980s to late 1990s. Taken together, the modeling results and empirical data suggest that highly elevated exposures to TCDD (i.e., body burdens in the several 100s of pg/g lipid range and greater) were not common among people inhabiting upland forest locations in SVN sprayed with AO and that peak and average body burdens were broadly similar to those of the general population of the U.S. in the 1970s and early 1980s. The model-based assessment is consistent with the 'hot spot' hypothesis i.e., potential exposures to TCDD linked to activities conducted on or near former bases where AO was stored are greater than potential exposures in areas subjected to aerial spraying.

  18. Comparison of mathematically-predicted toxic equivalents (TEQs) and bioassay-derived dioxin-equivalents (TCDD-EQs) in heron embryos

    Science.gov (United States)

    Rattner, B.; Hatfield, J.; Melancon, M.; Custer, T.; Tillitt, D.

    1995-01-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from an uncontaminated site (Chincoteague National Wildlife Refuge,VA) and three polluted sites (Cat Island, Green Bay, WI; Bair and West Marin Islands, San Francisco Bay, CA). Hepatic microsomal monooxygenases were induced up to 85-fold relative to the reference site, and was associated with concentrations of total PCBs and 11 PCB congeners that are presumed to concern.to express toxicity through the Ah receptor. TEQs [mathematically predicted; summed product of PCB congener concentrations using 5 different sets of toxic equivalency factors (TEFs)] were compared to TCDD-EQs [derived by bioassay; ethoxyresorufin-O-dealkylase activity of treated H411E rat hepatoma cells]. Although TEQs were up to 15-fold greater than TCDD-EQs, the pattern among sites was consistent and TEQs were highly correlated with TCDD-EQs. TEFs based on single congener mammalian studies yielded TEQs that greatly exceeded values from the H411E bioassay of field sample. TEFs generated from avian egg injection studies yielded TEQs that most closely approximated bioassay-derived TCDD-EQs. Cytochrome P450 parameters were related to TEQs and TCDD-EQs; adjusted r2 often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data document the general predictive value of TEQs and TCDD-EQs for P450 induction in field collected samples, but also indicate the need for development of TEFs for the species and biological end point of concern.

  19. In utero/lactational and adult exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) show differential effects on craniofacial development and growth in rats.

    Science.gov (United States)

    Sholts, Sabrina B; Korkalainen, Merja; Simanainen, Ulla; Miettinen, Hanna M; Håkansson, Helen; Viluksela, Matti

    2015-11-04

    In a previous study of female Han/Wistar (H/W) and Long-Evans (L-E) rats, we found that adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with size decreases in the cranium and especially the face. In this study we compared these crania to those from male and female Sprague-Dawley (S-D) rats with in utero/lactational exposure to TCDD, using morphometric variables of size, shape, and fluctuating asymmetry to quantify the effects of dose on craniofacial development and growth. At the highest levels of exposure, in utero/lactational and adult TCDD exposures both resulted in small but significant reductions in facial size parameters (i.e., 3-5%) in only females and minor effects on facial shape in both sexes. The shape effects of in utero/lactational exposure were most significant at the sutural intersections, whereas adult exposure to TCDD corresponded to dose-dependent changes of decreasing facial length and vault breadth. Fluctuating asymmetry in general explained a relatively small amount of shape variation compared with other effects, and only increased significantly in female L-E rats with high levels of adult exposure to TCDD. These results indicate that TCDD-related changes in cranial development and growth in rats can vary with the timing and duration of exposure, and with sex. Further investigations of other dioxin-like compounds and animal species will broaden our understanding of how chemicals exposure can influence the development and growth of the mammalian skeleton.

  20. TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts.

    Science.gov (United States)

    Henry, Ellen C; Welle, Stephen L; Gasiewicz, Thomas A

    2010-03-01

    The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1'H-indolo-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5muM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible.

  1. Effects of in ovo 2,3,7,8-TCDD exposure on hepatic ethoxyresorufin O-deethylase (EROD) induction and growth-related parameters in avian species

    Energy Technology Data Exchange (ETDEWEB)

    Janz, D.M.; Bellward, G.D. [Univ. of British Columbia, Vancouver, British Columbia (Canada). Faculty of Pharmaceutical Sciences

    1994-12-31

    The effects of early in ovo TCDD exposure on CYP1A1 induction and indices of growth were determined in domestic chicken (Gallus gallus) and pigeon (Columba livia) hatchlings. TCDD (in corn oil) was injected into the air sac of eggs on embryonic day 4 (E4) (chickens, 0.1 {mu}g/kg egg; pigeons, 1.0 {mu}g/kg egg), and on E14 (pigeons, 3.0 {mu}g/kg egg). In chickens, hepatic EROD was induced 13, 15, 34, and 43-fold above control activities on E19, day of hatch (DO), day 2 after hatch (D2), and D4, respectively. Plasma thyroid hormone (T{sub 3} T{sub 4}) concentrations, which are known to peak during the perinatal period in chickens, were not affected by TCDD treatment when measured on E17, E19, D0, D2, and D4. In pigeons injected on E4, EROD was induced 15 and 6-fold on D0 and D7, respectively. There were significant decreases in yolk-free body weight, crown-rump, tibia, culmen, and wing lengths, and an elevated liver to body weight ratio (LSI) in TCDD-treated pigeons raised to D7 (p < 0.01). In pigeons injected on E14 (3{mu}g/kg), EROD was induced 14 and 10-fold on D0 and D7, respectively. Crown-rump and culmen lengths were decreased (p < 0.05) and LSI was increased (p < 0.01) on D0. There were significant decreases in all morphological parameters, and an increased LSI on D7 (p < 0.01) in TCDD-treated birds. These techniques will be used in further studies to investigate possible mechanisms of TCDD embryotoxicity in wild avian species, such as the great blue heron (Ardea herodias).

  2. Anopheles arabiensis egg treatment with dieldrin for sex separation leaves residues in male adult mosquitoes that can bioaccumulate in goldfish (Carassius auratus auratus).

    Science.gov (United States)

    Yamada, Hanano; Jandric, Zora; Chhem-Kieth, Sorivan; Vreysen, Marc J B; Rathor, Mohammad N; Gilles, Jeremie R L; Cannavan, Andrew

    2013-12-01

    The sterile insect technique (SIT) is a biological control tactic that is used as a component of area-wide integrated pest management (AW-IPM) programs. The SIT can only be applied against disease-transmitting mosquitoes when only sterile male mosquitoes are released, and the blood-sucking and potentially disease-transmitting females are eliminated from the production line. For Anopheles arabiensis, a potent vector of malaria, a genetic sexing strain was developed whereby females can be eliminated by treating the eggs or larvae with the insecticide dieldrin. To evaluate the presence of dieldrin residues in male mosquitoes designated for SIT releases, a simple, sensitive, and accurate gas chromatography-electron capture detector (GC-ECD) method was developed. In addition, bioaccumulation and food chain transfer of these residues to fish after feeding with treated mosquitoes was demonstrated. The overall recovery from method validation studies was 77.3 ± 2.2% (mean ± relative standard deviation [RSD]) for the mosquitoes, and 99.1 ± 4.4% (mean ± RSD) for the fish. The average dieldrin concentration found in adult male An. arabiensis was 28.1 ± 2.9 µg/kg (mean ± standard deviation [SD]). A range of 23.9 ± 1.1 µg/kg to 73.9 ± 5.2 µg/kg (mean ± SD) of dieldrin was found in the fish samples. These findings indicate the need to reassess the environmental and health implications of control operations with a SIT component against An. arabiensis that involves using persistent organochlorines in the sexing process. © 2013 SETAC.

  3. Environmental neurotoxic pesticide dieldrin activates a non receptor tyrosine kinase to promote PKCδ-mediated dopaminergic apoptosis in a dopaminergic neuronal cell model.

    Science.gov (United States)

    Saminathan, Hariharan; Asaithambi, Arunkumar; Anantharam, Vellareddy; Kanthasamy, Anumantha G; Kanthasamy, Arthi

    2011-10-01

    Oxidative stress and apoptosis are two key pathophysiological mechanisms underlying dopaminergic degeneration in Parkinson's disease (PD). Recently, we identified that proteolytic activation of protein kinase C-delta (PKCδ), a member of the novel PKC family, contributes to oxidative stress-induced dopaminergic degeneration and that phosphorylation of tyrosine residue 311 (tyr311) on PKCδ is a key event preceding the PKCδ proteolytic activation during oxidative damage. Herein, we report that a non-receptor tyrosine kinase Fyn is significantly expressed in a dopaminergic neuronal N27 cell model. Exposure of N27 cells to the dopaminergic toxicant dieldrin (60 μM) rapidly activated Fyn kinase, PKCδ-tyr311 phosphorylation and proteolytic cleavage. Fyn kinase activation precedes the caspase-3-mediated proteolytic activation of PKCδ. Pre-treatment with p60-tyrosine-specific kinase inhibitor (TSKI) almost completely attenuated dieldrin-induced phosphorylation of PKCδ-tyr311 and its proteolytic activation. Additionally, TSKI almost completely blocked dieldrin-induced apoptotic cell death. To further confirm Fyn's role in the pro-apoptotic function of PKCδ, we adopted the RNAi approach. siRNA-mediated knockdown of Fyn kinase also effectively attenuated dieldrin-induced phosphorylation of PKCδ-tyr311, caspase-3-mediated PKCδ proteolytic cleavage, and DNA fragmentation, suggesting that Fyn kinase regulates the pro-apoptotic function of PKCδ. Collectively, these results demonstrate for the first time that Fyn kinase is a pro-apoptotic kinase that regulates upstream signaling of the PKCδ-mediated apoptotic cell death pathway in neurotoxicity models of pesticide exposure. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Comparison of TCDD-elicited genome-wide hepatic gene expression in Sprague–Dawley rats and C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Nault, Rance; Kim, Suntae; Zacharewski, Timothy R., E-mail: tzachare@msu.edu

    2013-03-01

    Although the structure and function of the AhR are conserved, emerging evidence suggests that downstream effects are species-specific. In this study, rat hepatic gene expression data from the DrugMatrix database (National Toxicology Program) were compared to mouse hepatic whole-genome gene expression data following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For the DrugMatrix study, male Sprague–Dawley rats were gavaged daily with 20 μg/kg TCDD for 1, 3 and 5 days, while female C57BL/6 ovariectomized mice were examined 1, 3 and 7 days after a single oral gavage of 30 μg/kg TCDD. A total of 649 rat and 1386 mouse genes (|fold change| ≥ 1.5, P1(t) ≥ 0.99) were differentially expressed following treatment. HomoloGene identified 11,708 orthologs represented across the rat Affymetrix 230 2.0 GeneChip (12,310 total orthologs), and the mouse 4 × 44K v.1 Agilent oligonucleotide array (17,578 total orthologs). Comparative analysis found 563 and 922 orthologs differentially expressed in response to TCDD in the rat and mouse, respectively, with 70 responses associated with immune function and lipid metabolism in common to both. Moreover, QRTPCR analysis of Ceacam1, showed divergent expression (induced in rat; repressed in mouse) functionally consistent with TCDD-elicited hepatic steatosis in the mouse but not the rat. Functional analysis identified orthologs involved in nucleotide binding and acetyltransferase activity in rat, while mouse-specific responses were associated with steroid, phospholipid, fatty acid, and carbohydrate metabolism. These results provide further evidence that TCDD elicits species-specific regulation of distinct gene networks, and outlines considerations for future comparisons of publicly available microarray datasets. - Highlights: ► We performed a whole-genome comparison of TCDD-regulated genes in mice and rats. ► Previous species comparisons were extended using data from the DrugMatrix database. ► Less than 15% of TCDD

  5. Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes

    OpenAIRE

    Kerkvliet, Nancy I.; Linda B. Steppan; Vorachek, William; Oda, Shannon; Farrer, David; Wong, Carmen P.; Pham, Duy; Mourich, Dan V.

    2009-01-01

    The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), is a novel inducer of adaptive Tregs. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent AHR ligand, induces adaptive CD4+CD25+ Tregs during an acute graft-versus-host (GvH) response and prevents the generation of allospecific cytotoxic T lymphocytes. TCDD also suppresses the induction of experimental autoimmune encephalitis in association with an expanded population of Foxp3+ Tregs. In this study, we show th...

  6. Influence of seasonality and exposure on the accumulation and reproductive effects of p,p'-dichlorodiphenyldichloroethane and dieldrin in largemouth bass.

    Science.gov (United States)

    Johnson, Kevin G; Muller, Jennifer K; Price, Bertram; Ware, Adam; Sepúlveda, María S; Borgert, Christopher J; Gross, Timothy S

    2007-05-01

    Two studies investigated the accumulation and reproductive effects of p,p'-dichlorodiphenyldichloroethane (DDE) and dieldrin over 30 or 120 d of oral exposure in captive Florida, USA, largemouth bass (Micropterus salmoides floridanus). The 30-d exposures were conducted during the peak reproductive season, and the 120-d study was conducted to simulate exposure throughout the ovarian cycle. Whole body chemical residue concentrations were similar, regardless of exposure duration, for the medium and high feed concentrations of either chemical; however, the low-dose residue concentrations were much lower, yet similar to natural exposures. No clear dose-response relationships were identified between chemical dose and morphological (length, weight, hepatosomatic index) or reproductive endpoints (sex steroid concentration, gonadosomatic index, percentage of fry hatching). Reproductive parameters were variable within treatment groups, indicating that circulating sex steroids and percent hatch endpoints have high natural variability among fish of the same age and reproductive stage. However, in general there was a decrease in plasma estradiol and 11-ketotestosterone for female and male fish, respectively, that were exposed to dieldrin. Overall, results suggest that exposure throughout ovarian (follicular) development to either DDE or dieldrin alone does not result in the depressed endocrine status and poor reproductive success reported in highly organochlorine pesticide-contaminated environments in Central Florida, USA.

  7. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces expression of p27(kip¹) and FoxO3a in female rat cerebral cortex and PC12 cells.

    Science.gov (United States)

    Xu, Guangfei; Liu, Jiao; Yoshimoto, Katsuhiko; Chen, Gang; Iwata, Takeo; Mizusawa, Noriko; Duan, Zhiqing; Wan, Chunhua; Jiang, Junkang

    2014-05-02

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent toxin that alters normal brain development, producing cognitive disability and motor dysfunction. Previous studies in rats have proved that female rats are more sensitive to TCDD lethality than male ones. Recent studies have shown that TCDD induces cell cycle arrest and apoptosis, but the regulatory proteins involved in these processes have yet to be elucidated. In this study, we constructed an acute TCDD injury female rat model, and investigated the effects of TCDD on apoptosis and expression of cell cycle regulators, forkhead box class O 3a (FoxO3a) and p27(kip1), in the central nervous system (CNS). Increased levels of active caspase-3 were observed in the cerebral cortex of female rats treated with TCDD, suggesting that TCDD-induced apoptosis occurs in the CNS. The terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling assay showed that apoptosis primarily occurred in neurons. Furthermore, Western blot analysis, reverse transcription-polymerase chain reaction, and immunohistochemistry showed a significant up-regulation of FoxO3a and p27(kip1) in the cerebral cortex. Immunofluorescent labeling indicated that FoxO3a and p27(kip1) were predominantly localized in apoptotic neurons, but not in astrocytes. In vitro experiments using PC12, a rat neuron-like pheochromocytoma cell line, also revealed that TCDD induced apoptosis and an increase in FoxO3a and p27(kip1) expression. Furthermore, knockdown of FoxO3a expression inhibited p27(kip1) transcription and TCDD-induced apoptosis. Based on our data, induction of FoxO3a may play an important role in TCDD-induced neurotoxicity.

  8. Removal of aldrin, dieldrin, heptachlor, and heptachlor epoxide using activated carbon and/or Pseudomonas fluorescens free cell cultures.

    Science.gov (United States)

    Bandala, Erick R; Andres-Octaviano, Juan; Pastrana, Paulino; Torres, Luis G

    2006-01-01

    Degradation of aldrin (1,2,3,4,10,10-Hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5-8-dimethanonaphthalene), heptachlor (1H-1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methano indene), dieldrin (1aalpha,2beta,2aalpha,3beta,6beta,6aalpha,7beta,7aalpha)-3,4,5,6,9,9-Hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-2,7:3,6-d-methanonaphtha[2,3-b]oxirene, and heptachlor epoxide (1aalpha, 1bbeta,2alpha,5alpha,5alphabeta,6beta,6aalpha-2,3,4,5,6,7,7-Heptachloro-1a,1b,5,5a,6,6a-hexahydro-2,5-methano-2H-inden[1,2-b]-oxirene) was tested using free cultures of Pseudomonas fluorescens under controlled conditions. Pesticide concentrations were monitored by gas chromatography during 120 h. Percentages of degradation and biodegradation rates (BDR) were calculated. Data showed a trend suggesting a relation between chemical structure and degradability. Degradation kinetics for each pesticide tested showed that the highest degradation rates were found in the first 24 h. Kinetics data were adjusted to an empirical equation in order to predict their behavior, and the correlation coefficients obtained were satisfactory. Gas chromatography/mass spectrometry (GC/MS) analysis of the final extracts allowed the identification of chlordene and monodechlorodieldrin, which have been reported as final metabolite produced in the biodegradation of this kind of compounds. Regarding adsorption of pesticides on activated vegetal carbon, we concluded that removal efficiencies between 95.45 and 97.18% can be reached, depending on the pesticide and the carbon dose applied. The values for K from the Freundlich equation were quite similar for the four pesticides (between 1.0001 and 1.04), whereas the n values were quite different for each pesticide in the following order of affinity: dieldrin > aldrin > heptachlor epoxide > heptachlor. Equilibrium times, very important for scaling up the process, were between 43 min and 1 h, for the heptachlor epoxide and the heptachlor, respectively.

  9. Long-term exposure to dieldrin reduces gamma-aminobutyric acid type A and N-methyl-D-aspartate receptor function in primary cultures of mouse cerebellar granule cells.

    Science.gov (United States)

    Babot, Zoila; Vilaró, M Teresa; Suñol, Cristina

    2007-12-01

    The organochlorine pesticide dieldrin is a persistent organic pollutant that accumulates in the fatty tissue of living organisms. In mammals, it antagonizes the GABA(A) receptor, producing convulsions after acute exposure. Although accumulation in human brain has been reported, little is known about the effects of long-term exposure to dieldrin in the nervous system. Homeostatic control of the balance between excitation and inhibition has been reported when neuronal activity is chronically altered. We hypothesized that noncytotoxic concentrations of dieldrin could decrease glutamatergic neurotransmission as a consequence of a prolonged reduction in GABA(A) receptor function. Long-term exposure of primary cerebellar granule cell cultures to 3 microM dieldrin reduced the GABA(A) receptor function to 55% of control, as measured by the GABA-induced (36)Cl(-) uptake. This exposure produced a significant reduction (approximately 35%) of the NMDA-induced increase in [Ca(2+)](i) and of the [(3)H]MK-801 binding, which was not accompanied by a reduction in the NMDA receptor subunit NR1, as determined by Western blot. Consistent with the decreased NMDA receptor function, dieldrin-treated cultures were insensitive to an excitotoxic stimulus induced by exposure to high potassium. In summary, we report that the chronic reduction of GABA(A) receptor function induced by dieldrin decreases the number of functional NMDA receptors, which may be attributable to a mechanism of synaptic scaling. These effects could underlie neural mechanisms involved in cognitive impairment produced by low-level exposure to dieldrin. (c) 2007 Wiley-Liss, Inc.

  10. 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Tcdd) Dose-Response Studies: Preliminary Literature Search Results and Request for Additional Studies

    Science.gov (United States)

    EPA invited the public to comment on the preliminary list of in vivo mammalian dose-response citations for 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). This list was compiled as a first step in the development of EPA’s response to the National Academy of Sciences comments (NAS, 2...

  11. Modeling of Ah-receptor dependent P450 induction I. Cellular model definition and its incorporation in a PBPK model of 2,3,7,8-TCDD

    NARCIS (Netherlands)

    Zeilmaker MJ; Eijkeren JCH van; LBO

    1997-01-01

    The interspecies extrapolation of chemical toxicity is traditionally based on the daily administered dose of the chemical. However, in the case of compounds with strong bioaccumulating properties, such as 2,3,7,8-TetraChloroDibenzo-p-Dioxin (TCDD), chronic toxicity is expected to scale better with t

  12. The Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD on the Mortality and Growth of Two Amphibian Species (Xenopus laevis and Pseudacris triseriata

    Directory of Open Access Journals (Sweden)

    Alex Collier

    2008-12-01

    Full Text Available We observed a slight drop in the growth of Xenopus laevis and Pseudacris triseriata larvae following acute exposure (24-48 h during egg development to three concentrations of TCDD (0.3, 3.0, 30.0 μg/l. Our exposure protocol was modeled on a previous investigation that was designed to mimic the effects of maternal deposition of TCDD. The doses selected were consistent with known rates of maternal transfer between mother and egg using actual adult body burdens from contaminated habitats. Egg and embryonic mortality immediately following exposure increased only among 48 h X. laevis treatments. Control P. triseriata and X. laevis completed metamorphosis more quickly than TCDDtreated animals. The snout-vent length of recently transformed P. triseriata did not differ between treatments although controls were heavier than high-dosed animals. Likewise, the snout-vent length and weight of transformed X. laevis did not differ between control and TCDD treatments. These findings provide additional evidence that amphibians, including P. triseriata and X. laevis are relatively insensitive to acute exposure to TCDD during egg and embryonic development. Although the concentrations selected for this study were relatively high, they were not inconsistent with our current understanding of bioaccumulation via maternal transfer.

  13. Modeling of Ah-receptor dependent P450 induction I. Cellular model definition and its incorporation in a PBPK model of 2,3,7,8-TCDD

    NARCIS (Netherlands)

    Zeilmaker MJ; van Eijkeren JCH; LBO

    1997-01-01

    De extrapolatie van de toxiciteit van chemische stoffen van proefdieren naar de mens vindt traditioneel plaats op basis van de dagelijks toegediende hoeveelheid van een stof. Echter, voor stoffen met sterk accumulerende eigenschappen zoals 2,3,7,8-TetraChloroDibenzo-p-Dioxine (TCDD) ligt een extrap

  14. EGF AND TGF ALPHA EXPRESSION INFLUENCE THE DEVELOPMENTAL TOXICITY OF TCDD: DOSE RESPONSE AND AHR PHENOTYPE IN EGF, TGF ALPHA AND EGF+TGF ALPHA KNOCKOUT MICE

    Science.gov (United States)

    Abstract The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate (CP) and hydronephrosis (HN) in mice. The etiology of these defects involves hyperproliferation of epithelial cells of the secondary palatal shelf and ureter, respectively. ...

  15. LACK OF EXPRESSION OF EGF AND TGF-ALPHA IN THE FETAL MOUSE ALTERS FORMATION OF PROSTATIC EPITHELIAL BUDS AND INFLUENCES THE RESPONSE TO TCDD

    Science.gov (United States)

    Lack of Expression of EGF and TGF in the Fetal Mouse Alters Formation of Prostatic Epithelial Buds and Responsiveness to TCDD-Induced Impairment of Prostatic Bud Formation. Barbara D. Abbott, Tien-Min Lin, Nathan T. Rasmussen, Robert W. Moore,Ralph M. Albrecht, Judi...

  16. EMERGING TECHNOLOGY REPORT: BENCH-SCALE TESTING OF PHOTOLYSIS, CHEMICAL OXIDATION AND BIODEGRADATION OF PCB CONTAMINATED SOILS AND PHOTOLYSIS OF TCDD CONTAMINATED SOILS

    Science.gov (United States)

    This report presents the results of bench-scale testing on degradation of 2,3,7,8-TCDD using W photolysis, and PCB degradation using UV photolysis, chemical oxidation and biological treatment. Bench-scale tests were conducted to investigate the feasibility of a two-phase detoxifi...

  17. 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Tcdd) Dose-Response Studies: Preliminary Literature Search Results and Request for Additional Studies

    Science.gov (United States)

    EPA invited the public to comment on the preliminary list of in vivo mammalian dose-response citations for 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). This list was compiled as a first step in the development of EPA’s response to the National Academy of Sciences comments (NAS, 2...

  18. Influence of TCDD and natural Ah receptor agonists on benzo[a]pyrene-DNA adduct formation in the Caco-2 human colon cell line

    NARCIS (Netherlands)

    Waard, de W.J.; Kok, de T.M.C.M.; Maas, L.M.; Peijnenburg, A.A.C.M.; Hoogenboom, L.A.P.; Aarts, H.J.M.; Schooten, van F.J.

    2008-01-01

    Several compounds originating from cruciferous vegetables and citrus fruits bind to and activate the aryl hydrocarbon receptor (AhR). This receptor plays an important role in the toxicity of the known tumour promoter and potent AhR-agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, vegetab

  19. Exposure of human JEG-3 cell line to TCDD alters progesterone secretion but does not act on their viability and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Augustowska, K.; Gregoraszczuk, E.L. [Jagiellonian Univ., Krakow (Poland)

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds are lipophilic and difficult to metabolize. Any environmental exposure of living organisms to these congeners results in their accumulation in fat tissue and bioconcentration in humans via the food chain. TCDD acts as an endocrine disrupter to alter differentiation and function of the reproductive system. Therefore, these compounds represent a serious health risk, especially to the fetus and infants, whose enzymatic and metabolic systems are not yet mature. Our previous data showed high accumulation of TCDD in cultured human placental tissue which caused a decrease in hormone secretion. However, the mechanism of this action is still unclear. JEG-3 cell line from malignant placental tissue has been used as an in vitro model for investigation of the effects of xenobiotics on placenta toxicity. These cells are morphologically similar to their origin, the trophoblast of the normal first trimester placenta, and produce many peptides and steroid hormones found in normal trophoblast cells, such as hCG, GhRH, progesterone. The aim of the present study was firstly, to show dose- and time-dependent effects of TCDD on progesterone production by JEG-3 cells and secondly, to examine mechanism of its action on cell viability and apoptosis.

  20. EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGFALPHA KO FETAL MOUSE PALATE

    Science.gov (United States)

    EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGF" KO FETAL MOUSE PALATE. Abbott, Barbara D.1; Boyd, Hadiya2; Wood, Carmen1; Held, Gary1. 1.EPA, ORD, NHEERL, RTD, US EPA, Research Triangle Park, NC, USA. 2MARC Program, NCCU, Durham, NC, USA. <...

  1. The influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hematological parameters during experimentally induced pleuritis in rats.

    Science.gov (United States)

    Całkosiński, Ireneusz; Rosińczuk-Tonderys, Joanna; Bazan, Justyna; Dzierzba, Katarzyna; Całkosińska, Monika; Majda, Jacek; Dobrzyński, Maciej; Bronowicka-Szydełko, Agnieszka

    2013-04-01

    Proper functioning of homeostatic mechanisms is characteristic for every healthy organism and enables adapting to environmental changes. These complicated systematic reactions can neutralize the harmful stress factors leading to various inflammatory reactions. The aim of this study was to determine dynamic changes in the inflammatory reaction after single 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration of 5 μg/kg body weight into rats with experimentally induced pleuritis. These changes were observed by monitoring the hematological blood parameters during inflammation. The obtained results proved that dioxins contribute to various changes in the character of the inflammatory response. TCDD administration before pleuritis initiation caused an increase of lymphocytes and significant decrease of the number of neutrophils during inflammation. The current study proved that administration of low TCDD dose (seven times lower than used in other studies) can cause thymus, spleen, or lymphatic gland atrophy. This finding indicates the toxic influence of small TCDD dose especially on the immune system.

  2. Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells.

    Science.gov (United States)

    Joiakim, Aby; Mathieu, Patricia A; Shelp, Catherine; Boerner, Julie; Reiners, John J

    2016-05-01

    CYP1A1 and CYP1A2 are transcriptionally activated in the human normal breast epithelial cell line MCF10A following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Shifting MCF10A cultures to medium deficient in serum and epidermal growth factor (EGF) caused rapid reductions in the activated (i.e., phosphorylated) forms of extracellular regulated kinases (ERKs) and the epidermal growth factor receptor (EGFR). Shifting to serum/EGF-deficient medium also enhanced TCDD-mediated induction of cytochrome P450 (CYP)1A1 Treatment of cells cultured in complete medium with the EGFR inhibitors gefitinib (Iressa), AG1478, and CI-1033 resulted in concentration-dependent reductions of active EGFR and ERKs, and increased CYP1A1 mRNA content ∼3- to 18-fold above basal level. EGFR inhibitors synergized with TCDD and resulted in transient CYP1A1 and CYP1A2 mRNA accumulations ∼8-fold greater (maximum at 5 hours) than that achieved with only TCDD. AG1478, gefitinib, and TCDD individually induced small increases (∼1.2- to 2.5-fold) in CYP1A1 protein content but did not cause additive or synergistic accumulations of CYP1A1 protein when used in combination. The mitogen-activated protein kinase kinase inhibitor PD184352 inhibited ERK and EGFR activation in a concentration-dependent fashion without causing CYP1A1 mRNA accumulation. However, cotreatment with PD184352 potentiated TCDD-mediated CYP1A1 induction. TCDD-mediated induction of CYP1A1 in MCF7-TET on-EGFR cells, a MCF7 variant in which EGFR expression can be controlled, was not affected by the activity status of EGFR or ERKs. Hence, EGFR signaling mutes both basal and ligand-induced expression of two aryl hydrocarbon receptor-responsive P450s in MCF10A cultures. However, these effects are cell context-dependent. Furthermore, CYP1A1 mRNA and protein abundance are not closely coupled in MCF10A cultures.

  3. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

    Directory of Open Access Journals (Sweden)

    Jacob Aude

    2011-08-01

    Full Text Available Abstract Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP or Δ9-tetrahydrocannabinol (Δ9-THC. Results After ex vivo exposure to TCDD (a highly potent AhR ligand for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold and Cyp1b1 protein (2-fold in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression Conclusions Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

  4. Interactive effects of n-TiO2 and 2,3,7,8-TCDD on the marine bivalve Mytilus galloprovincialis.

    Science.gov (United States)

    Canesi, Laura; Frenzilli, Giada; Balbi, Teresa; Bernardeschi, Margherita; Ciacci, Caterina; Corsolini, Simonetta; Della Torre, Camilla; Fabbri, Rita; Faleri, Claudia; Focardi, Silvano; Guidi, Patrizia; Kočan, Anton; Marcomini, Antonio; Mariottini, Michela; Nigro, Marco; Pozo-Gallardo, Karla; Rocco, Lucia; Scarcelli, Vittoria; Smerilli, Arianna; Corsi, Ilaria

    2014-08-01

    Despite the growing concern over the potential biological impact of nanoparticles (NPs) in the aquatic environment, little is known about their interactions with other pollutants. The bivalve Mytilus sp, largely utilized as a sentinel for marine contamination, has been shown to represent a significant target for different types of NP, including n-TiO2, one of the most widespread in use. In this work, the possible interactive effects of n-TiO2 and 2,3,7,8-TCDD, chosen as models of NP and organic contaminant, respectively, were investigated in Mytilus galloprovincialis. In vitro experiments with n-TiO2 and TCDD, alone and in combination, were carried out in different conditions (concentrations and times of exposure), depending on the target (hemocytes, gill cells and biopsies) and the endpoint measured. Mussels were also exposed in vivo to n-TiO2 (100 μg L(-1)) or to TCDD (0.25 μg L(-1)), alone and in combination, for 96 h. A wide range of biomarkers, from molecular to tissue level, were measured: lysosomal membrane stability and phagocytosis in hemocytes, ATP-binding cassette efflux transporters in gills (gene transcription and efflux activity), several biomarkers of genotoxicity in gill and digestive cells (DNA damage, random amplified polymorphic DNA-RAPD changes), lysosomal biomarkers and transcription of selected genes in the digestive gland. The results demonstrate that n-TiO2 and TCDD can exert synergistic or antagonistic effects, depending on experimental condition, cell/tissue and type of measured response. Some of these interactions may result from a significant increase in TCDD accumulation in whole mussel organisms in the presence of n-TiO2, indicating a Trojan horse effect. The results represent the most extensive data obtained so far on the sub-lethal effects of NPs and organic contaminants in aquatic organisms. Moreover, these data extend the knowledge on the molecular and cellular targets of NPs in bivalves.

  5. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects tooth development in rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Iku; Kazuhiro, Tsuga; Yasumasa, Akagawa [Hiroshima Univ. (Japan); Mineo, Yasuda; Hiroshi, Sumida [Hiroshima International Univ. (Japan); Akihiro, Arima; Toshio, Ihara [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan); Shunichiro, Kubota [Tokyo Univ. (Japan); Kazuo, Asaoka [Kyoto Univ., Inuyama (Japan). Primate Research Institute; Takumi, Takasuga [Shimadzu Techno-Research Inc., Kyoto (Japan)

    2004-09-15

    The current tolerable daily intake (TDI) of dioxin and dioxin related compounds has been set at 4 pg TEQ/kg/day in Japan. This value was calculated from the lowest-observed-adverse-effect level (LOAEL) in experimental animals, mostly rodents. Gray et al. reported that a single oral dose of 200 ng/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pregnant rats on day 15 of gestation resulted in abnormalities of reproductive organs in the offspring. The maternal body burden at this dose was measured to be 86 ng/kg. To attain this body burden level, human daily intake was calculated to be 43.6 pg/kg/day. An uncertainty factor of 10 was applied to this value, and the human TDI was established. However, due to great differences in the biological half life of TCDD between human and rodents, the validity of this calculation is questioned. To obtain more reliable LOAEL in the second generation, we initiated a long-term study in rhesus monkeys in 1999. In rodents, teeth are known to be targets of developmental toxicity of dioxin. In utero and lactational TCDD exposure affects rat incisor and molar development. In humans also tooth abnormalities were reported among populations exposed to dioxins. In our monkey experiment, some young were stillborn or died neonatally. These animals provided us with a unique opportunity to study tooth development in primate young exposed to TCDD in utero and lactationally. By macroscopic observation we found some tooth abnormalities among died young exposed to TCDD5. This prompted us to examine surviving young by radiography. This is an interim report of our findings in these young.

  6. BRCA-1 promoter hypermethylation and silencing induced by the aromatic hydrocarbon receptor-ligand TCDD are prevented by resveratrol in MCF-7 cells.

    Science.gov (United States)

    Papoutsis, Andreas J; Borg, Jamie L; Selmin, Ornella I; Romagnolo, Donato F

    2012-10-01

    Epigenetic mechanisms may contribute to reduced expression of the tumor suppressor gene BRCA-1 in sporadic breast cancers. Through environmental exposure and diet, humans are exposed to xenobiotics and food compounds that bind the aromatic hydrocarbon receptor (AhR). AhR-ligands include the dioxin-like and tumor promoter 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). The activated AhR regulates transcription through binding to xenobiotic response elements (XREs=GCGTG) and interactions with transcription cofactors. Previously, we reported on the presence of several XREs in the proximal BRCA-1 promoter and that the expression of endogenous AhR was required for silencing of BRCA-1 expression by TCDD. Here, we document that in estrogen receptor-α-positive and BRCA-1 wild-type MCF-7 breast cancer cells, the treatment with TCDD attenuated 17β-estradiol-dependent stimulation of BRCA-1 protein and induced hypermethylation of a CpG island spanning the BRCA-1 transcriptional start site of exon-1a. Additionally, we found that TCDD enhanced the association of the AhR; DNA methyl transferase (DNMT)1, DNMT3a and DNMT3b; methyl binding protein (MBD)2; and trimethylated H3K9 (H3K9me3) with the BRCA-1 promoter. Conversely, the phytoalexin resveratrol, selected as a prototype dietary AhR antagonist, antagonized at physiologically relevant doses (1 μmol/L) the TCDD-induced repression of BRCA-1 protein, BRCA-1 promoter methylation and the recruitment of the AhR, MBD2, H3K9me3 and DNMTs (1, 3a and 3b). Taken together, these observations provide mechanistic evidence for AhR agonists in the establishment of BRCA-1 promoter hypermethylation and the basis for the development of prevention strategies based on AhR antagonists.

  7. Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. In vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man and a non-human primate (Callithrix jacchus)

    Energy Technology Data Exchange (ETDEWEB)

    Neubert, R.; Helge, H. (Freie Univ. Berlin (Germany, F.R.). Kinderklinik und Poliklinik); Jacob-Mueller, U.; Stahlmann, R.; Neubert, D. (Freie Univ. Berlin (Germany, F.R.). Inst. fuer Toxikologie und Embryonalpharmakologie)

    1991-04-01

    The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on poke weed mitogen-stimulated proliferation and differentiation of peripheral lymphocytes was studied in vitro with cells from a non-human primate (marmoset monkey, Callithrix jacchus) and from man. Monoclonal antibodies and flow cytometry (FACScan) were used for analysis. The extent of the overall mitogen-stimulated proliferation of isolated lymphocytes in vitro from marmoset blood was only slightly reduced in the presence of TCDD compared to the solvent control (0.01% DMSO). However, incubation with TCDD in the culture medium together with the mitogen led to a pronounced decrease in the percentage of the lymphocyte subset with the surface marker CD4, and a concomitant increase in the percentage of CD8{sup +} cells. The lowest concentration found to be effective in vitro was 1x10{sup -13} M TCDD (25 fg TCDD/ml). When culturing lymphocytes from human blood of different donors under indentical conditions in the presence of TCDD and the mitogen, corresponding effects were observed to those seen with marmoset cells. A closer analysis of the T lymphocyte subsets affected revealed the CD4{sup +}CDw29{sup +} (helper-inducer cells) to be the main target for the action of TCDD. A clear-cut change in the percentage of this subpopulation was induced at concentrations as low as 1x10{sup -13} M TCDD. The development of the IL-2-marker in culture was only slightly affected by TCDD, and concentrations of 1x10{sup -12} M were required to slightly reduce the number of CD2{sup +}CD25{sup +} cells. Special B cells, namely CD20{sup +} (i.e. B{sub 1}) cells, were found to be especially susceptible to the action of TCDD, and clear-cut effects were seen in several experimental series at 1x10{sup -14} M TCDD. The formation of B cells with IgG lambda or kappa chains was also depressed in culture in the presence of TCDD. (orig./MG).

  8. Exposure to p,p′-DDE or dieldrin during the reproductive season alters hepatic CYP expression in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Barber, David S.; McNally, Alex J.; Garcia-Reyero, Natàlia; Denslow, Nancy D.

    2007-01-01

    Largemouth bass (LMB) in Central Florida living on sites with high levels of organochlorine pesticides (OCPs) have exhibited poor reproductive success and altered steroid profiles. The mechanism underlying these changes is unknown, however changes in the rate of steroid metabolism could alter steroid homeostasis. Members of the CYP2 and CYP3A families play a significant role in the metabolism of many xenobiotics and endogenous compounds, including sex steroids. Therefore, the goal of this study was to identify members of the CYP2 and CYP3A families in LMB and characterize the effects of OCP exposure on their expression. Full-length clones of two CYP3A isoforms were obtained from LMB liver, CYP3A68 and 3A69, which exhibited significant sequence divergence. Full-length clones for CYP2N14 and CYP2P11 were also obtained from LMB liver. Steady-state mRNA levels of each of these CYPs increased in both sexes between early reproductive phase (December) and peak reproductive phase (March). Expression of CYP3A68 and CYP2P11 was sexually dimorphic during peak reproductive phase with 2-fold higher expression in females and males, respectively. Foodborne exposure to 46 ppm p,p′-DDE or 0.8 ppm dieldrin for 30 days did not have a significant effect on expression of CYPs. However, 4 months exposure to p,p′-DDE induced CYP3A68 and 3A69 expression in both sexes, while dieldrin produced weak induction of CYP3A68 and suppressed CYP3A69 expression in females, but had no effect on males. Neither p,p′-DDE nor dieldrin significantly altered the expression of CYP2P11 or CYP2N14. This work demonstrates that there are significant changes in CYP expression that occur during LMB reproduction which can be modified by exposure to OCPs. PMID:17145087

  9. Exposure to p,p'-DDE or dieldrin during the reproductive season alters hepatic CYP expression in largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Barber, David S; McNally, Alex J; Garcia-Reyero, Natàlia; Denslow, Nancy D

    2007-02-15

    Largemouth bass (LMB) in Central Florida living on sites with high levels of organochlorine pesticides (OCPs) have exhibited poor reproductive success and altered steroid profiles. The mechanism underlying these changes is unknown, however changes in the rate of steroid metabolism could alter steroid homeostasis. Members of the CYP2 and CYP3A families play a significant role in the metabolism of many xenobiotics and endogenous compounds, including sex steroids. Therefore, the goal of this study was to identify members of the CYP2 and CYP3A families in LMB and characterize the effects of OCP exposure on their expression. Full-length clones of two CYP3A isoforms were obtained from LMB liver, CYP3A68 and 3A69, which exhibited significant sequence divergence. Full-length clones for CYP2N14 and CYP2P11 were also obtained from LMB liver. Steady-state mRNA levels of each of these CYPs increased in both sexes between early reproductive phase (December) and peak reproductive phase (March). Expression of CYP3A68 and CYP2P11 was sexually dimorphic during peak reproductive phase with 2-fold higher expression in females and males, respectively. Foodborne exposure to 46 ppm p,p'-DDE or 0.8 ppm dieldrin for 30 days did not have a significant effect on expression of CYPs. However, 4 months exposure to p,p'-DDE induced CYP3A68 and 3A69 expression in both sexes, while dieldrin produced weak induction of CYP3A68 and suppressed CYP3A69 expression in females, but had no effect on males. Neither p,p'-DDE nor dieldrin significantly altered the expression of CYP2P11 or CYP2N14. This work demonstrates that there are significant changes in CYP expression that occur during LMB reproduction which can be modified by exposure to OCPs.

  10. Spatial distribution of CYP2B1/2 messenger RNA within the rat liver acinus following exposure to the inducers phenobarbital and dieldrin.

    Science.gov (United States)

    Dail, Mary B; Burgess, Shane C; Meek, Edward C; Wagner, Jennifer; Baravik, Jeffrey; Chambers, Janice E

    2007-09-01

    Traditionally, the liver has been considered a homogeneous organ, but literature suggests that the cytochromes P450 are differentially distributed among the hepatocytes and that the pattern of this distribution is altered by various xenobiotics. In this study, the CYP2B1/2 messenger RNA (mRNA) in the hepatocytes was compared following treatment of rats with either of two inducers, phenobarbital (PB), or dieldrin. Adult male Sprague-Dawley-derived rats were treated with either ip PB in saline at 80 mg/kg/day for 5 days or dieldrin in corn oil by oral gavage at 2.5 mg/kg/day for 13 days. Control rats received ip saline or po corn oil for the same time. Laser capture microdissection (LCM) followed by duplex quantitative real-time reverse transcriptase PCR was used to measure the CYP2B1/2 mRNA produced in bands of hepatocytes isolated from three locations along the sinusoidal path. The amounts of mRNA present in whole liver subsamples were also analyzed. CYP2B1/2 enzyme activity was determined by assaying 16beta-hydroxytestosterone formation. Whole liver mRNA samples exhibited significant induction in CYP2B1/2 transcript levels: sixfold for PB and 2200-fold for dieldrin. All the LCM band samples also showed significant fold induction in CYP2B1/2 mRNA compared to controls. Dieldrin caused marked increases in CYP2B1/2 mRNA levels in the direction of blood flow through the acinus: periportal, 300-fold; midzonal, 600-fold; and centrilobular, 1700-fold. A different pattern of induction was observed in the PB-treated rats: periportal, 1800-fold; midzonal, 8800-fold; and centrilobular, 1600-fold. The present study indicates the differences in spatial responses that can be exhibited within the liver following exposure to various xenobiotics. It also indicates the importance of examining xenobiotic metabolism in the liver in light of its nonhomogeneous, zoned microenvironment.

  11. Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

    Science.gov (United States)

    Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

    2016-11-01

    Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.

  12. Distribution pathways of hexachlorocyclohexane isomers in a soil-plant-air system. A case study with Cynara scolymus L. and Erica sp. plants grown in a contaminated site.

    Science.gov (United States)

    Pereira, R Calvelo; Monterroso, C; Macías, F; Camps-Arbestain, M

    2008-09-01

    This study focuses on the main routes of distribution and accumulation of different hexachlorocyclohexane (HCH) isomers (mainly alpha-, beta-, gamma- and delta-HCH) in a soil-plant-air system. A field assay was carried out with two plant species, Cynara scolymus L. and Erica sp., which were planted either: (i) directly in the HCH-contaminated soil; or (ii) in pots filled with uncontaminated soil, which were placed in the HCH-contaminated soil. Both plant species accumulated HCH in their tissues, with relatively higher accumulation in above-ground biomass than in roots. The beta-HCH isomer was the main isomer in all plant tissues. Adsorption of HCH by the roots from contaminated soil (soil-->root pathway) and adsorption through the aerial biomass from either the surrounding air, following volatilization of the contaminant (soil-->air-->shoot pathway), and/or contact with air-suspended particles contaminated with HCH (soil particles-->shoot pathway) were the main mechanisms of accumulation. These results may have important implications for the use of plants for reducing the transfer of contaminants via the atmosphere.

  13. Study of the genotoxic and cytotoxic effects of the α-, β-, and γ- Hexachlorocyclohexane isomers in human lymphocyte cells using the cytokinesis-block micronucleus assay.

    Science.gov (United States)

    Ennaceur, Soukaina

    2017-01-01

    The genotoxic potential of hexachlorocyclohexane (HCH) isomers (α-, β-, and γ-) which are organochlorine pesticides was tested in peripheral blood lymphocyte cultures from two donors by using the cytokinesis-block micronucleus assay. Micronucleus (MN) frequency, binucleated cells with micronucleus (BNMN), and cytokinesis-blocked proliferation index (CBPI) were determined as genotoxic and cytotoxic endpoints. At the concentration ranges tested (12.5-100 μg.L (-1)), all HCH isomers induced dose-dependent cytotoxic effects, γ-HCH being the most toxic. This isomer was also able to induce significant increase in MN frequency and BNMN cells indicating a genotoxic potential at 50 and 100 μg.L (-1). The genotoxic test of β-HCH showed a positive induction of MN and BNMN cells at the highest concentration of 100 μg.L (-1) and a significant cytotoxicity at 50 μg.L (-1). Under the experimental condition used, α-HCH was unable to induce any significant increase in MN frequency confirming that α-HCH is a non-genotoxic agent.

  14. Application of a level IV fugacity model to simulate the long-term fate of hexachlorocyclohexane isomers in the lower reach of Yellow River basin, China.

    Science.gov (United States)

    Ao, Jiangting; Chen, Jingwen; Tian, Fulin; Cai, Xiyun

    2009-01-01

    A level IV multimedia fugacity model was established to simulate the fate and transfer of hexachlorocyclohexane (HCH) isomers in the lower reach of the Yellow River basin, China, during 1952-2010. The predicted concentrations of HCHs are in good agreement with the observed ones, as indicated by the residual errors being generally lower than 0.5 logarithmic units. The effects of extensive agricultural application and subsequent prohibition of HCHs are reflected by the temporal variation of HCHs predicted by the model. It is predicted that only 1.8 tons of HCHs will be left in 2010, less than 0.06% of the highest contents (in 1983) in the study area, and about 99% of HCHs remain in soil. The proportions of HCH isomers in the environment also changed with time due to their different physicochemical properties. Although beta-HCH is not the main component of the technical HCHs, it has become the most abundant isomer in the environment because of its persistence. The dominant transfer processes between the adjacent compartments were deposition from air to soil, air diffusion through the air-water interface and runoff from soil to water. Sensitivity analysis showed that degradation rate in soil, parameters related to major sources, and thickness of soils had the strongest influence on the model result. Results of Monte Carlo simulation indicated the overall uncertainty of model predictions, and the coefficients of variation of the estimated concentrations of HCHs in all the compartments ranged from 0.5 to 5.8.

  15. Diverse neurotoxicants converge on gene expression for neuropeptides and their receptors in an in vitro model of neurodifferentiation: effects of chlorpyrifos, diazinon, dieldrin and divalent nickel in PC12 cells.

    Science.gov (United States)

    Slotkin, Theodore A; Seidler, Frederic J

    2010-09-24

    Unrelated developmental neurotoxicants can produce similar neurobehavioral outcomes. We examined whether disparate agents affect neuromodulators that control numerous neurotransmitters and circuits, employing PC12 cells to explore the targeting of neuroactive peptides by organophosphates (chlorpyrifos, diazinon), an organochlorine (dieldrin) and a metal (Ni(2+)); we utilized microarrays to profile gene expression for the peptides and their receptors. Chlorpyrifos evoked robust upregulation of cholecystokinin, corticotropin releasing hormone, galanin, neuropeptide Y, neurotensin, preproenkephalin and tachykinin 1; this involved a critical period at the commencement of neurodifferentiation, since the effects were much less notable in undifferentiated PC12 cells. Diazinon targeted a similar but smaller repertoire of neuropeptide genes and the magnitude of the effects was also generally less. Surprisingly, dieldrin shared many of the same neuropeptide targets as the organophosphates and concordance analysis showed significant overlap among all three pesticides. However, dieldrin had more notable effects on neuropeptide receptors, and overlap between diazinon and dieldrin for the receptors led to a stronger resemblance of these two agents than of chlorpyrifos and dieldrin. Ni(2+) was unique, evoking upregulation of only one of the peptides affected by the other agents, while causing downregulation of several others. Nevertheless, there was still significant concordance between Ni(2+) and either diazinon or dieldrin, reflecting similarities toward the receptors. Our results show that neuropeptides are likely to be a prominent target for the developmental neurotoxicity of organophosphates and other neurotoxicants, and further, that the convergence of disparate agents on the same genes and pathways may contribute to similar neurobehavioral outcomes. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression.

    Directory of Open Access Journals (Sweden)

    Narendra P Singh

    Full Text Available BACKGROUND: MicroRNAs (miRs are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, an environmental contaminant is well known to induce severe toxicity (acute and chronic with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand "the fetal basis of adult disease" hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes. METHODOLOGY/PRINCIPAL FINDINGS: miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3'-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected. CONCLUSIONS/SIGNIFICANCE: These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and

  17. Biodegradation of 2,3,7,8 TCDD by anaerobic and aerobic microcosms collected from bioremediation treatments for cleaning up dioxin contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Dang Thi; Tuan, Mai Anh; Viet, Nguyen Quoc; Sanh, Nguyen Thi [Vietnamese Academy of Science and Technology (VAST) (Viet Nam). Inst. of Biotechnology; Sau, Trinh Khac [Vietnam-Russian Tropical Center (Viet Nam); Papke, O. [ERGO Forschungsgesellschaft, Hamburg (Germany)

    2004-09-15

    There are many microbes that can degrade polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurants (PCDFs) and polychlorinated biphenyls (PCBs) have been isolated including purified bacteria, actinomycetes, white rods, filamentous fungi, anaerobes and also anaerobic and aerobic consortia. Bioremediation one of biological remediation has been studied as hopeful alternative to physical and chemical treatments that using for cleaning up PCDDs, PCDFs. In Vietnam for cleaning up ''hot spot'' of some former military air bases, bioremediation has been studying in different scales of Danang site. After 18 to 24 month treatments, the reduction of toxicity was significally detected. In order to study biodegradability by different groups and one of dominated strain that are existing microorganisms in our treatments, the investigation of 2,3,7,8 TCDD anaerobic and aerobic degradations was carried out in the laboratory condition. Anaerobic microbial consortium containing three different bacteria such as two Gram- negative vibrio and rod and one gram positive cocoides bacteria. This consortium could degrade 118 pg TEQ/ml 2,3,7,8 TCDD after 133 days under sulfate reduction. Concentration of 2,3,7,8 TCDD in the soil extract that adding to medium at starting point of cultivation was 144.6 pg TEQ/ml. About 81% toxicity was removed. Aerobic consortium containing all three Gram-negative bacteria and one fungal strain. After 9 day shaking at 180 rpm/min and 30 C, 85.6 % of 164.45 pg TEQ/ml 2,3,7,8 TCDD was removed. Other preliminary results of study of 2,3,7,8 TCDD biodegradation as sole carbon and energy by show that this strain FDN30 could remove 43,45 pg TEQ/ml (59%) of 73,1 pgTEQ/ml adding dioxin after two weeks. These findings explain why high concentration of contaminants in treated soil was decreased after two year treatment. Indigenous microorganisms play leading role in the detoxification of 2,3,7,8 TCDD in contaminated soils.

  18. Biodegradation of 2,3,7,8 TCDD by anaerobic and aerobic microcosms collected from bioremediation treatments for cleaning up dioxin contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Dang Thi; Tuan, Mai Anh; Viet, Nguyen Quoc; Sanh, Nguyen Thi [Vietnamese Academy of Science and Technology (VAST) (Viet Nam). Inst. of Biotechnology; Sau, Trinh Khac [Vietnam-Russian Tropical Center (Viet Nam); Papke, O. [ERGO Forschungsgesellschaft, Hamburg (Germany)

    2004-09-15

    There are many microbes that can degrade polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurants (PCDFs) and polychlorinated biphenyls (PCBs) have been isolated including purified bacteria, actinomycetes, white rods, filamentous fungi, anaerobes and also anaerobic and aerobic consortia. Bioremediation one of biological remediation has been studied as hopeful alternative to physical and chemical treatments that using for cleaning up PCDDs, PCDFs. In Vietnam for cleaning up ''hot spot'' of some former military air bases, bioremediation has been studying in different scales of Danang site. After 18 to 24 month treatments, the reduction of toxicity was significally detected. In order to study biodegradability by different groups and one of dominated strain that are existing microorganisms in our treatments, the investigation of 2,3,7,8 TCDD anaerobic and aerobic degradations was carried out in the laboratory condition. Anaerobic microbial consortium containing three different bacteria such as two Gram- negative vibrio and rod and one gram positive cocoides bacteria. This consortium could degrade 118 pg TEQ/ml 2,3,7,8 TCDD after 133 days under sulfate reduction. Concentration of 2,3,7,8 TCDD in the soil extract that adding to medium at starting point of cultivation was 144.6 pg TEQ/ml. About 81% toxicity was removed. Aerobic consortium containing all three Gram-negative bacteria and one fungal strain. After 9 day shaking at 180 rpm/min and 30 C, 85.6 % of 164.45 pg TEQ/ml 2,3,7,8 TCDD was removed. Other preliminary results of study of 2,3,7,8 TCDD biodegradation as sole carbon and energy by show that this strain FDN30 could remove 43,45 pg TEQ/ml (59%) of 73,1 pgTEQ/ml adding dioxin after two weeks. These findings explain why high concentration of contaminants in treated soil was decreased after two year treatment. Indigenous microorganisms play leading role in the detoxification of 2,3,7,8 TCDD in contaminated soils.

  19. Aryl hydrocarbon receptor regulates CYP1B1 but not ABCB1 and ABCG2 in hCMEC/D3 human cerebral microvascular endothelial cells after TCDD exposure.

    Science.gov (United States)

    Jacob, Aude; Potin, Sophie; Chapy, Hélène; Crete, Dominique; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier

    2015-07-10

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor activated by a variety of widespread persistent environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It can transactivate the expression of several target genes. Recently AhR transcripts were detected in isolated human brain microvessels and in the hCMEC/D3 human cerebral microvascular endothelial cell line, an in vitro model of the human cerebral endothelium. To date AhR implication in the co-regulation of ABCB1, ABCG2 and CYP1B1 at human cerebral endothelium has not been addressed. Here we investigated whether AhR could co-regulate ABCB1, ABCG2 and CYP1B1 expressions in the hCMEC/D3 cell line. Exposure to TCDD induced a concentration-dependent increase in CYP1B1 expression. We demonstrated AhR involvement in the TCDD-mediated increase in CYP1B1 expression by using small interfering RNA against AhR. Western blotting analysis also revealed an increase in CYP1B1 protein expression following TCDD exposure in hCMEC/D3. Regarding ABCB1 and ABCG2, exposure to TCDD had no effect on their protein expressions and functional activities. In conclusion our data indicated a differential modulation of CYP1B1 and ABCB1/ABCG2 expressions in hCMEC/D3 cells following TCDD exposure.

  20. Very low-dose (femtomolar) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts steroidogenic enzyme mRNAs and steroid secretion by human luteinizing granulosa cells.

    Science.gov (United States)

    Baldridge, M G; Marks, G T; Rawlins, R G; Hutz, R J

    2015-04-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic congener of the polyhalogenated aromatic hydrocarbons (PAH), which causes anatomical abnormalities and developmental defects, impairs ovulation and reduces fertility. TCDD's endocrine-disrupting effects are, in part, caused by a direct action at the ovary. Herein we investigated the in-vitro effects of environmentally relevant doses of TCDD on estradiol-17β (E2) production by human luteinizing granulosa cells (hLGC) obtained from women stimulated for in-vitro fertilization (IVF). TCDD at all concentrations tested (3.1fM, 3.1pM and 3.1nM) significantly decreased E2 secretion when assayed for by radioimmunoassay (RIA). Herein we confirm that TCDD alters E2 secretion by hLGC in a time-, not dose-dependent fashion and are the first to show decreases in E2 secretion with fM concentrations of TCDD. Using real-time quantitative PCR (RT-qPCR), the decreased E2 secretion correlates with a decrease in the mRNA expression levels two enzymes in the estrogen biosynthesis pathway: CYP11A1 and CYP19A1.

  1. Aldrin and dieldrin: a review of research on their production, environmental deposition and fate, bioaccumulation, toxicology, and epidemiology in the United States.

    Science.gov (United States)

    Jorgenson, J L

    2001-01-01

    In the last decade four international agreements have focused on a group of chemical substances known as persistent organic pollutants (POPs). Global agreement on the reduction and eventual elimination of these substances by banning their production and trade is a long-term goal. Negotiations for these agreements have focused on the need to correlate data from scientists working on soil and water sampling and air pollution monitoring. Toxicologists and epidemiologists have focused on wildlife and human health effects and understanding patterns of disease requires better access to these data. In the last 20 years, substantial databases have been created and now are becoming available on the Internet. This review is a detailed examination of 2 of the 12 POPs, aldrin and dieldrin, and how scientific groups identify and measure their effects. It draws on research findings from a variety of environmental monitoring networks in the United States. An overview of the ecologic and health effects of aldrin and dieldrin provides examples of how to streamline some of the programs and improve access to mutually useful scientific data. The research groups are located in many government departments, universities, and private organizations. Identifying databases can provide an "information accelerator" useful to a larger audience and can help build better plant and animal research models across scientific fields. PMID:11250811

  2. Protein kinase C is a target for diverse developmental neurotoxicants: transcriptional responses to chlorpyrifos, diazinon, dieldrin and divalent nickel in PC12 cells.

    Science.gov (United States)

    Slotkin, Theodore A; Seidler, Frederic J

    2009-03-31

    Unrelated developmental neurotoxicants can elicit similar functional outcomes, whereas agents in the same class may differ. We compared two organophosphate insecticides (chlorpyrifos, diazinon) with an organochlorine (dieldrin) and a metal (Ni(2+)) for similarities and differences in their effects on gene expression encoding subtypes of protein kinase C and their modulators, a cell signaling cascade that integrates the actions of neurotrophic factors involved in brain development. We conducted evaluations in PC12 cells, a model for neuronal development, with each agent introduced at 30 microM for 24 or 72 h, treatments devoid of cytotoxicity. Chlorpyrifos evoked by far the largest effect, with widespread upregulation of multiple genes; the effects were greater during neurodifferentiation than when cells were exposed prior to differentiation. Diazinon had smaller and less widespread effects, consistent with its lesser long-term impact on synaptic function and behavior noted for in vivo exposures in developing rats. Surprisingly, the effects of diazinon, dieldrin and Ni(2+) showed basic similarities despite the fact that all three come from different classes of toxicants. Our findings provide some of the first evidence for a specific mechanistic cascade contributing to the cholinesterase-independent developmental neurotoxicant actions of chlorpyrifos and its differences from diazinon, while at the same time identifying mechanistic convergence between otherwise unrelated toxicants that provides predictions about common neurodevelopmental outcomes. These results further show how combined use of cell cultures and microarray technology can guide future in vivo work on diverse developmental neurotoxicants.

  3. The adverse effects of aldrin and dieldrin on both myometrial contractions and the secretory functions of bovine ovaries and uterus in vitro.

    Science.gov (United States)

    Wrobel, Michał H; Grzeszczyk, Marlena; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2015-05-15

    Aldrin and dieldrin are chloroorganic insecticides which are recognised as endocrine disruptors. The aim of the study was to investigate their effect on the secretory functions of the uterus and ovary and on myometrial contractions. Myometrial strips and uterine and ovarian cells from nonpregnant cows were incubated with the xenobiotics (0.1, 1 or 10 ng/ml) for 24 or 72 h. Next, their effect on viability of myometrial, endometrial, granulosa and luteal cells, myometrial strip contractions, the synthesis and secretion of prostaglandins (PGs: PGF2α and PGE2) from uterine cells, the secretion of oestradiol (E2), testosterone (T) and oxytocin (OT) from granulosa cells and the secretion of progesterone (P4) and OT from luteal cells were determined. Neither of the xenobiotics (10 ng/ml) affected (P>0.05) the viability of the ovarian and uterine cells, while both (0.1-10 ng/ml) decreased (P0.05) the synthesis and the secretion of PGs from the myometrial cells. Although they also did not impair the secretion of the PGs from the endometrial cells, they abolished (Pdieldrin stimulated secretion of E2 and T from the granulosa cells, while only dieldrin increased (Pdieldrin stimulated the secretory function of the cultured granulosa and luteal cells and inhibited the myometrial contractions of cows in vitro, which may affect on natural parturition. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Dieldrin-induced neurotoxicity involves impaired mitochondrial bioenergetics and an endoplasmic reticulum stress response in rat dopaminergic cells.

    Science.gov (United States)

    Schmidt, Jordan T; Rushin, Anna; Boyda, Jonna; Souders, Christopher Laurence; Martyniuk, Christopher J

    2017-08-24

    Mitochondria are sensitive targets of environmental chemicals. Dieldrin (DLD) is an organochlorine pesticide that remains a human health concern due to high lipid bioaccumulation, and it has been epidemiologically associated to an increased risk for Parkinson's disease (PD). As mitochondrial dysfunction is involved in the etiology of PD, this study aimed to determine whether DLD impaired mitochondrial bioenergetics in dopaminergic cells. Rat immortalized dopaminergic N27 cells were treated for 24 or 48h with one dose of either a solvent control, 2.5, 25, or 250μM DLD. Dopaminergic cells treated with 250μM DLD showed increased Casp3/7 activity at 24 and 48h. DLD also caused a dose dependent reduction in cell viability of ∼25-30% over 24h. No significant effects on cell viability, apoptosis, nor cytotoxicity were detected at 24 or 48h with 2.5μM DLD. Following a 24h exposure to 2.5 and 25μM DLD, viable cells were subjected to a mitochondrial stress test using the Seahorse XFe24 Extracellular Flux Analyzer. Following three independent experiments conducted for rigor, dopaminergic cells that were treated with 2.5 and 25μM DLD consistently showed a reduction in maximum respiration and spare capacity compared to the control group. Molecular responses were measured to determine mechanisms of DLD-induced mitochondrial dysfunction. There were no changes in transcripts associated with mitochondrial membrane potential and permeability (e.g. Ant, Hk1, Tspo, Vdac), nor PI3 K/Akt/mTor signaling or mitochondrial-associated apoptotic factors (Bax, Bcl2, Casp3). However, transcript levels for Chop/Gadd153 (DNA Damage Inducible Transcript 3), an apoptotic gene activated following endoplasmic reticulum (ER) stress, were 3-fold higher in N27 cells treated with DLD, suggesting that DLD-induced mitochondrial dysfunction is related to ER stress. Dopamine cells were also assessed for changes in tyrosine hydroxylase (TH) protein, which did not differ among treatments. This study

  5. Defining suitable reference genes for RT-qPCR analysis on human sertoli cells after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

    Science.gov (United States)

    Ribeiro, Mariana Antunes; dos Reis, Mariana Bisarro; de Moraes, Leonardo Nazário; Briton-Jones, Christine; Rainho, Cláudia Aparecida; Scarano, Wellerson Rodrigo

    2014-11-01

    Quantitative real-time RT-PCR (qPCR) has proven to be a valuable molecular technique to quantify gene expression. There are few studies in the literature that describe suitable reference genes to normalize gene expression data. Studies of transcriptionally disruptive toxins, like tetrachlorodibenzo-p-dioxin (TCDD), require careful consideration of reference genes. The present study was designed to validate potential reference genes in human Sertoli cells after exposure to TCDD. 32 candidate reference genes were analyzed to determine their applicability. geNorm and NormFinder softwares were used to obtain an estimation of the expression stability of the 32 genes and to identify the most suitable genes for qPCR data normalization.

  6. EZR1: a novel family of highly expressed retroelements induced by TCDD and regulated by a NF-κB-like factor in embryos of zebrafish (Danio rerio).

    Science.gov (United States)

    Goldstone, Heather M H; Tokunaga, Saimi; Schlezinger, Jennifer J; Goldstone, Jared V; Stegeman, John J

    2012-03-01

    Transcript profiling using a zebrafish heart cDNA library previously revealed abundant expressed sequence tags (ESTs) upregulated in zebrafish embryos treated with the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Here, we identify those ESTs as LTR-containing retroelements termed EZR1 (Expressed-Zebrafish-Retroelement group 1). EZR1 is highly redundant in the genome and includes canonical long terminal repeats (LTRs) flanking an integrase-like open reading frame and a region similar to retroviral envelope protein genes. EZR1 sequences lack reverse transcriptase, RNase H, or protease, indicating retrotransposition would be nonautonomous. No AHR binding motifs were found in the EZR1 promoter region. A putative NF-κB-binding site was found, and TCDD-treated zebrafish embryos had significantly increased levels of nuclear protein(s) binding to this sequence. Protein-EZR1 DNA complex formation was partially competed by a mammalian consensus κB sequence, consistent with NF-κB-like activation contributing to increased protein binding to this site. Mobility of the TCDD-induced protein-EZR1 complex differed from that of authentic NF-κB protein bound to the consensus κB site. The results suggest that EZR1 is regulated by interaction with NF-κB or NF-κB-like protein(s) different from the NF-κB protein binding to the consensus κB site. The nature of the NF-κB-like protein and the relationship between EZR1 induction and cardiovascular toxicity caused by TCDD warrant further investigation.

  7. EZR1: A Novel Family of Highly Expressed Retroelements Induced by TCDD and Regulated by a NF-κB-Like Factor in Embryos of Zebrafish (Danio rerio)

    OpenAIRE

    2012-01-01

    Transcript profiling using a zebrafish heart cDNA library previously revealed abundant expressed sequence tags (ESTs) upregulated in zebrafish embryos treated with the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Here, we identify those ESTs as LTR-containing retroelements termed EZR1 (Expressed-Zebrafish-Retroelement group 1). EZR1 is highly redundant in the genome and includes canonical long terminal repeats (LTRs) flanking an integrase-like open readi...

  8. Lack of direct immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human peripheral blood lymphocyte subsets in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lang, D.S. (Center for Environmental Medicine and Lung Biology, Univ. of North Carolina, Chapel Hill, NC (United States)); Becker, S. (TCR-Environmental Corp., Inc., Chapel Hill, NC (United States)); Clark, G.C. (National Inst of Environmental Health Science, Lab. of Biochemical Risk Analysis, RTP, NC (United States)); Devlin, R.B. (US Environmental Protection Agency, Health Effects Research Lab., RTP, NC (United States)); Koren, H.S. (US Environmental Protection Agency, Health Effects Research Lab., RTP, NC (United States))

    1994-05-01

    The direct effects of dioxin on human PBL subpopulations have been studied, in order to determine their usefulness as sensitive biomarkers for human dioxin exposure. Lymphocyte cultures from healthy individuals were treated with 10[sup -7] M-10[sup -14] M TCDD in the absence and presence of stimulation with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody (moAb; OKT3) for 3 days. Cytochrome P450 (CYP1A1) enzyme induction, one of the best studied direct biological effects of TCDD on numerous cell types, was assayed in parallel by ethoxyresorufin-O-deethylase (EROD) activity. Percentages of the different lymphocytes subsets, including CD2 (T cells); CD4; CD45 RA (subpressor-inducer/virgin T cells); CD4 CD29; CD8; CD19 (B cells) as well as interleukin 2 (IL-2) receptor (CD25) and class II antigen (HLA-DR) expression, were analyzed by flow cytometry. DNA synthesis was determined by [sup 3]H-thymidine uptake after 3 days of culture. In the present study, all stimulated lymphocyte cultures showed a dose-dependent significant increase of CYP1A1 activity at dioxin concentrations of 10[sup -7] and 10[sup -9] M. No enzyme activity could be detected at lower concentrations of TCDD. On the other hand, neither alteration in surface marker distribution nor suppression of lymphocyte proliferation could be demonstrated in mitogen-activated cells following any concentration of TCDD treatment. These data suggest that the inducibility of CYP1A1 enzyme activity is not correlated with direct immunotoxic effects in vitro in human PBL. (orig./MG)

  9. The Influence of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Hematological Parameters During Experimentally Induced Pleuritis in Rats

    OpenAIRE

    Całkosiński, Ireneusz; Rosińczuk-Tonderys, Joanna; Bazan, Justyna; Dzierzba, Katarzyna; Całkosińska, Monika; Majda, Jacek; Dobrzyński, Maciej; Bronowicka-Szydełko, Agnieszka

    2012-01-01

    Proper functioning of homeostatic mechanisms is characteristic for every healthy organism and enables adapting to environmental changes. These complicated systematic reactions can neutralize the harmful stress factors leading to various inflammatory reactions. The aim of this study was to determine dynamic changes in the inflammatory reaction after single 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration of 5 μg/kg body weight into rats with experimentally induced pleuritis. These cha...

  10. TCDD-Induced Activation of Aryl Hydrocarbon Receptor Inhibits Th17 Polarization and Regulates Non-Eosinophilic Airway Inflammation in Asthma

    OpenAIRE

    Xiao-ming Li; Juan Peng; Wen Gu; Xue-jun Guo

    2016-01-01

    The aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, has recently been demonstrated to regulate T cell differentiation. Whether AhR activation participates in allergic airway inflammation remains unknown. In the current study, using a non-eosinophilic asthma model, we demonstrate that 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD), a potent AhR ligand, reduced the airway infiltration of neutrophils, airway hyperresponsiveness and Th17 cytokine expression. Further...

  11. Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells

    Directory of Open Access Journals (Sweden)

    Burgoon Lyle D

    2011-04-01

    Full Text Available Abstract Background 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD is an environmental contaminant that elicits a broad spectrum of toxic effects in a species-specific manner. Current risk assessment practices routinely extrapolate results from in vivo and in vitro rodent models to assess human risk. In order to further investigate the species-specific responses elicited by TCDD, temporal gene expression responses in human HepG2, mouse Hepa1c1c7 and rat H4IIE cells were compared. Results Microarray analysis identified a core set of conserved gene expression responses across species consistent with the role of AhR in mediating adaptive metabolic responses. However, significant species-specific as well as species-divergent responses were identified. Computational analysis of the regulatory regions of species-specific and -divergent responses suggests that dioxin response elements (DREs are involved. These results are consistent with in vivo rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches. Conclusions Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with in vivo rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.

  12. PCB153, TCDD and estradiol compromise the benzo[a]pyrene-induced p53-response via FoxO3a.

    Science.gov (United States)

    Al-Anati, Lauy; Kadekar, Sandeep; Högberg, Johan; Stenius, Ulla

    2014-08-05

    TCDD, polychlorinated biphenyls (PCB) and polycyclic aromatic hydrocarbons (PAH) coexist in the environment. However, there are few studies on combined effects of these compounds. We have studied the effect of TCDD, PCB153 and estradiol on p53 signaling induced by PAHs. We show that all three compounds amplified the accumulation of nuclear p53, elicited by benzo[a]pyrene (BaP) or dibenzo[al]pyrene (DBP). This effect was associated with an attenuated PAH-induced apoptosis and with decreased levels of phosphorylated FoxO3a Thr32. Thr32 phosphorylation of FoxO3a may promote a translocation of FoxO3a-p53 complex from nucleus to the cytoplasm, and the role of FoxO3a dephosphorylation was further studied. We found that inhibition of PP2A phosphatase restored levels of phosphorylated FoxO3a, led to cytosolic translocation of p53, and activated BaP-induced p53-mediated apoptosis. These results were confirmed by silencing FoxO3a with siRNA or by inhibiting 14-3-3 protein; also these treatments trapped BaP-induced p53 in the nucleus. Our data indicate interplay between p53, FoxO3a and 14-3-3 leading to an attenuated BaP induced apoptosis in cells co-exposed to TCDD, PCB 153 or estradiol.

  13. Reductive dechlorination of alpha-, beta-, delta-, and gamma-hexachlorocyclohexane isomers by hydroxocobalamin in the presence of either dithiothreitol or titanium(III) citrate as reducing agents.

    Science.gov (United States)

    Rodríguez-Garrido, B; Arbestain, M Camps; Monterroso, M C; Macías, F

    2004-10-01

    The effect of the reducing potential on the reductive dehalogenation of the different HCH (hexachlorocyclohexane) isomers has not yet been studied. In the present study, the potential for dehalogenation of (alpha-, beta-, delta-, and gamma-HCH isomers by the dithiothreitol (DTT) and titanium(III) citrate (reducing potential at pH 7, -0.33 and -0.48 V, respectively), with and without the addition of hydroxocobalamin was investigated. In the presence of DTT without catalyst, there was no disappearance of any of the HCH isomers studied after 1 h of treatment. However, disappearance of the gamma- and alpha-HCH isomers was observed during the same time period when titanium(III) citrate was used as the reductant in the absence of catalyst (62.9 and 16.6% disappearance, respectively). Addition of the hydroxocobalamin to the DTT system favored mainly the disappearance of gamma- and alpha-HCH (92.9 and 30.8% disappearance after 1 h, respectively); disappearance of delta-HCH and beta-HCH was small (11.9%) or negligible, respectively. Addition of the hydroxocobalamin to the titanium(III) citrate system favored the degradation of all HCH isomers under study: beta- and alpha-HCH completely disappeared to undetectable levels ( alpha-HCH > delta-HCH > beta-HCH, coincided with a decreasing order of the axially positioned Cl atoms of these isomers (considering their thermodynamically most stable configuration). This study is the first description of the rapid degradation of delta- and beta-HCH under abiotic conditions, and the results demonstrate the effect of the reducing potential on the reductive dehalogenation of HCH isomers.

  14. Bacterial diversity and real-time PCR based assessment of linA and linB gene distribution at hexachlorocyclohexane contaminated sites.

    Science.gov (United States)

    Lal, Devi; Jindal, Swati; Kumari, Hansi; Jit, Simran; Nigam, Aeshna; Sharma, Pooja; Kumari, Kirti; Lal, Rup

    2015-03-01

    The disposal of hexachlorocyclohexane (HCH) muck has created large number of HCH dumpsites all over the world from where the harmful HCH isomers are leaking into the environment. Bacteria have evolved at such contaminated sites that have the ability to degrade HCH. Degradation of various HCH isomers in bacterial strains is mediated primarily by two genes: linA and linB which encode dehydrochlorinase and haloalkane dehalogenase respectively. In this study we explored one such highly contaminated HCH dumpsite located in Lucknow, Uttar Pradesh, India. To assess the biostimulation potential of the contaminated site, microbial diversity study and real-time PCR based quantification of lin genes was carried out. The soil samples from dumpsite and surrounding areas were found to be highly contaminated with HCH residue levels as high as 1.8 × 10(5)  mg kg(-1). The residues were detected in areas upto 13 km from the dumpsite. Sphingomonads, Chromohalobacter, and Marinobacter were the dominant genera present at the dump-site. Role of Sphingomonads in HCH degradation has been well documented. The highest copy numbers of linA and linB genes as determined using real-time PCR were 6.2 × 10(4) and 5.3 × 10(5), respectively, were found in sample from the dump site. The presence of Sphingomonads, linA, and linB genes from HCH contaminated soil indicates the presence of indigenous bacterial communities capable of HCH degradation.

  15. Enantiomer-specific biomagnification of alpha-hexachlorocyclohexane and selected chiral chlordane-related compounds within an Arctic marine food web.

    Science.gov (United States)

    Hoekstra, Paul F; O'Hara, Todd M; Karlsson, Heidi; Solomon, Keith R; Muir, Derek C

    2003-10-01

    Concentrations of achiral and chiral organochlorine contaminants (OCs), including hexachlorocyclohexane isomers (HCH), chlordane congeners (cis- and trans-chlordane, cis- and trans-nonachlor, MC5, MC7, and U82), and related metabolites (oxychlordane [OXY] and heptachlor exo-epoxide [HEPX]), were quantified in seawater (100 L; n = 6) and biota from the coastal Beaufort-Chukchi Seas food web near Barrow (AK, USA). The biota included zooplankton (Calanus spp.; n = 5), fish species such as arctic cod (Boreogadus saida; n = 10), arctic char (Salvelinus alpinus; n = 3), and marine mammals including bowhead whales (Balaena mysticetus; liver: n = 23; blubber: n = 40), beluga whales (Delphinapterus leucas; blubber: n = 20), ringed seals (Phoca hispida; blubber: n = 20), and bearded seals (Erignathus barbatus; blubber: n = 7). The food web magnification factors (FWMFs) for HCHs and chlordane compounds ranged from 0.5 (gamma-HCH) to 6.5 (HEPX) and were expected based on known recalcitrance and biotransformation of OCs. The enantiomer fractions (EFs) of all chiral OCs were near racemic (EF = 0.50) in the seawater, zooplankton, and all fish analyzed. In contrast, the EFs for most OCs analyzed were nonracemic (EF # 0.50) in the marine mammals blubber (range: 0.09-0.79) because of enantiomer-specific biotransformation and (or) accumulation. However, EF values were not significantly correlated with isotopically determined trophic level. The EFs for all chiral OCs (except alpha-HCH) in bowhead whale liver closely approximated the values in zooplankton, suggesting that the accumulation of chiral OCs from prey into this cetacean is not enantiomer specific. However, the modification of EFs from bowhead liver to blubber suggests that this species has the ability to enantioselectively biotransform and accumulate several chiral OC compounds.

  16. A 50-years record of dichloro-diphenyl-trichloroethanes and hexachloro-cyclohexanes in lake sediments and penguin droppings on King George Island,Maritime Antarctic

    Institute of Scientific and Technical Information of China (English)

    SUN Li-guang; YIN Xue-bin; PAN Can-ping; WANG Yu-hong

    2005-01-01

    Since the ban on the use of organochlorine pesticides (OCPs) such as dichloro-diphenyl-trichloroethane (DDT) and hexachlorocyclohexane(HCH) in agriculture, their levels have generally dropped. In a number of cases, however, the levels of these OCPs were found to be unchanging or even increasing after the ban. With the aim to unveil the possible causes of these exceptions, we collected two lake cores from King George Island, West Antarctica, and determined their accumulation flux profiles and temporal trends of these OCPs. In the lake core sediments with glacier meltwater input, the accumulation flux of DDT shows an abnormal peak around 1980s in addition to the expected one in 1960s. In the lake core sediments without glacier meltwater input, the accumulation flux of DDT shows a gradual decline trend after the peak in 1960s. This striking difference in the DDT flux profiles between the two lake cores is most likely caused by the regional climate warming and the resulted discharge of the DDT stored in the Antarctic ice cap into the lakes in the Antarctic glacier frontier. Furthermore, to investigate the change of OCPs loadings in the Antarctic coastal ecosystem, we reconstructed the HCH and DDT concentration profiles in penguin droppings and observed a gradual increase for the former and a continuous decrease for the latter during the past 50 years. The increase of HCH seems to be due to the regional warming from the early 1970s and the resulted HCH discharge to the coastal ecosystem by glaciers, meltwater and the illegal use of HCH in the Southern Hemisphere in the recent decade.The different temporal trends of HCH and DDT accumulation rate in the lake core with glacier meltwater input and the aged penguin droppings can be explained by their different water-soluble property.

  17. Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

    Directory of Open Access Journals (Sweden)

    Matthews Jason

    2011-07-01

    Full Text Available Abstract Background The aryl hydrocarbon receptor (AhR is a ligand-activated transcription factor (TF that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS. AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR, extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'. Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t > 0.999. Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation.

  18. Effects of 2,3,7,8-TCDD and benzo[a]pyrene on modulating vitellogenin expression in primary culture of crucian carp (Carassius auratus) hepatocytes

    Institute of Scientific and Technical Information of China (English)

    LIANG Yong; C. K. C. Wong; XU Ying; M. H. Wong

    2004-01-01

    Vitellogenin (Vtg) is the precursor of yolk protein. Its expression and secretion are estrogen-regulated and are crucial for oocyte maturation. An in vitro xenoestrogen screening model was established by measuring Vtg induction in cultured primary hepatocytes from crucian carp. Vtg production was detected by biotin-avidin sandwich ELISA method while Vtg and cytochrome P4501A1 (CYP1A1) mRNA induction were measured by semi- quantitative PCR-primer dropping technique. Vtg and Vtg mRNA were dose-dependently induced by diethylstilbestrol (DES, 0.2-200 ng/mL) in hepatocytes of crucian carp. Co-treatment of the DES-induced hepatocytes with either 2,3,7,8-TCDD (TCDD, 0.1-4 pg/mL) or benzo[a]pyrene (B[a]P, 5-1000 ng/mL) resulted in a reduction of Vtg production and an increment of CYP1A1 mRNA expression both in a dose dependent manner, indicating the anti-estro-genic effects of the compounds. However, at lower tested concentrations, TCDD (0.1, 0.2 pg/mL), B[a]P (5 ng/mL) seemed to have a potentiating effect on Vtg expression and secretion, although by their own these compounds had no observable estrogenic effect on Vtg induction. Tamoxifen (a selective estrogen receptor modulators, 1 nmol/L-1 μmol/L), and β-naphtho-flavone (β-NF, an aryl hydrocarbon receptor inducing compounds, 2.5-1000 ng/mL) also were employed to study the possible interactions in DES-induced Vtg expression. In co-treatment of the DES-induced hepatocytes with β-NF or tamoxifen, the decrease in Vtg production did parallel induction of CYP1A1 for β-NF, but tamoxifen inhibited Vtg induction did not parallel induced CYP1A1 expression in all test concentrations. On the contrary, it was found that in co-treatment of the TCDD-induced hepatocytes with DES, TCDD induced CYP1A1 mRNA production was inhibited by DES also. These results implicated a possible cross talk between estrogen receptor- and aryl hydrocarbon receptor-mediated pathways in the hepatocytes.

  19. Proteomic analysis of human bladder epithelial cells by 2D blue native SDS-PAGE reveals TCDD-induced alterations of calcium and iron homeostasis possibly mediated by nitric oxide.

    Science.gov (United States)

    Verma, Nisha; Pink, Mario; Petrat, Frank; Rettenmeier, Albert W; Schmitz-Spanke, Simone

    2015-01-02

    A proteomic analysis of the interaction among multiprotein complexes involved in 2,3,7,8-dibenzo-p-dioxin (TCDD)-mediated toxicity in urinary bladder epithelial RT4 cells was performed using two-dimensional blue native SDS-PAGE (2D BN/SDS-PAGE). To enrich the protein complexes, unexposed and TCDD-exposed cells were fractionated. BN/SDS-PAGE of the resulting fractions led to an effective separation of proteins and protein complexes of various origins, including cell membrane, mitochondria, and other intracellular compartments. Major differences between the proteome of control and exposed cells involved the alteration of many calcium-regulated proteins (calmodulin, protein S100-A2, annexin A5, annexin A10, gelsolin isoform b) and iron-regulated proteins (ferritin, heme-binding protein 2, transferrin). On the basis of these findings, the intracellular calcium concentration was determined, revealing a significant increase after 24 h of exposure to TCDD. Moreover, the concentration of the labile iron pool (LIP) was also significantly elevated in TCDD-exposed cells. This increase was strongly inhibited by the calmodulin (CaM) antagonist W-7, which pointed toward a possible interaction between iron and calcium signaling. Because nitric oxide (NO) production was significantly enhanced in TCDD-exposed cells and was also inhibited by W-7, we hypothesize that alterations in calcium and iron homeostasis upon exposure to TCDD may be linked through NO generated by CaM-activated nitric oxide synthase. In our model, we propose that NO produced upon TCDD exposure interacts with the iron centers of iron-regulatory proteins (IRPs) that modulate the alteration of ferritin and transferrin, resulting in an augmented cellular LIP and, hence, increased toxicity.

  20. Utilizing thin-film solid-phase extraction to assess the effect of organic carbon amendments on the bioavailability of DDT and dieldrin to earthworms

    Science.gov (United States)

    Andrade, Natasha A.; Centofanti, Tiziana; McConnell, Laura L.; Hapeman, Cathleen J.; Torrents, Alba; Anh, Nguyen; Beyer, W. Nelson; Chaney, Rufus L.; Novak, Jeffrey M.; Anderson, Marya O.; Cantrell, Keri B.

    2014-01-01

    Improved approaches are needed to assess bioavailability of hydrophobic organic compounds in contaminated soils. Performance of thin-film solid-phase extraction (TF-SPE) using vials coated with ethylene vinyl acetate was compared to earthworm bioassay (Lumbricus terrestris). A DDT and dieldrin contaminated soil was amended with four organic carbon materials to assess the change in bioavailability. Addition of organic carbon significantly lowered bioavailability for all compounds except for 4,4′-DDT. Equilibrium concentrations of compounds in the polymer were correlated with uptake by earthworms after 48d exposure (R2 = 0.97; p 40yr of aging. Results show that TF-SPE can be useful in examining potential risks associated with contaminated soils and to test effectiveness of remediation efforts.

  1. Analysis of in vitro metabolites of 2,3,7,8-TCDD in rat liver microsomes by LC-ESI-MS/MS%2,3,7,8-TCDD代谢产物的液-质联用分析

    Institute of Scientific and Technical Information of China (English)

    王春艳; 唐志; 宋凤瑞; 蔡宗苇

    2013-01-01

    采用肝微粒体体外温孵法,对2,3,7,8-TCDD在大鼠肝微粒体中进行体外代谢研究。利用实验中所建立的液相色谱串联质谱方法对其代谢产物进行直接分析,共鉴别出两类代谢产物,分别为2个单羟基化代谢产物(2-OH-1,3,7,8-TCDD和1-OH-2,3,7,8-TCDD)和双羟基化脱氯的代谢产物。%2,3,7,8-TCDD is potentially harmflu to human and animal health. The aim of this study is to identify metabolites of 2,3,7,8-TCDD from the in vitro metabolism using rat liver microsome P450 enzymes. We had indentified two kinds of metabolites of 2,3,7,8-TCDD by using liquid chromatography coupled with tandem mass spectrometry,namely,monohydroxylated metabolites of 2,3,7,8-TCDD and trichloro-dihydroxydibenzo-p-dioxins.

  2. Research on hexachlorocyclohexane and dichlorodiphenyltrichloroethane residues in domestic water%生活用水中六六六和滴滴涕的残留分析

    Institute of Scientific and Technical Information of China (English)

    高雪; 王翠芬; 刘萍; 刘晓慧; 颜红; 谢英; 冉升

    2015-01-01

    Objective To determine the content of hexachlorocyclohexane (BHC) and dichlorodiphenyltrichloroethane (DDT) by gas chromatography in the tap water, bottled water, pure water and distilled water, so as to study the pollution resulted by BHC and DDT in different kinds of domestic water. Methods By using the method of liquid-liquid extraction, the BHC and DDT were extracted with petroleum ether from water firstly. They were concentrated with pressure blowing concentration secondly. Then, the analysis was detected by gas chromatography with ECD detector, and quantified the sample by external standard. Result The BHC and DDT were detected in different life water. The detectable rates ofβ-BHC and o,p′-DDT were 100%, the detectable rate of α-BHC was 75%, and the content of BHC and DDT in the pure water and bottled water were low. Conclusion The long-term harm caused by the high chemical stability and persistent of BHC and DDT can not be ignored.%目的:利用气相色谱法测定自来水、桶装水、纯水、蒸馏水中的六六六和滴滴涕含量,研究六六六和滴滴涕对不同生活用水污染情况。方法采用液液萃取方法,用石油醚提取水中六六六和滴滴涕,氮吹仪浓缩后用气相色谱仪 ECD 检测器检测,外标法定量。结果不同生活用水中六六六和滴滴涕均有检出,其中β-BHC、o,p′-DDT检出率为100%,α-BHC检出率为75%,纯水中和桶装水中含量较低。结论六六六、滴滴涕由于其化学性质稳定及高残留性所引起的远期危害不容忽视。

  3. Rhizobium rosettiformans sp. nov., isolated from a hexachlorocyclohexane dump site, and reclassification of Blastobacter aggregatus Hirsch and Muller 1986 as Rhizobium aggregatum comb. nov.

    Science.gov (United States)

    Kaur, Jaspreet; Verma, Mansi; Lal, Rup

    2011-05-01

    A Gram-negative, rod-shaped, motile, aerobic bacterial strain, W3(T), was isolated from hexachlorocyclohexane (HCH)-contaminated groundwater from Lucknow, India, and its taxonomic position was determined using a polyphasic approach. Strain W3(T) shared highest 16S rRNA gene sequence similarity of 97.8 % with Rhizobium selenitireducens B1(T), followed by Rhizobium daejeonense L61(T) (97.7 %), Rhizobium radiobacter ATCC 19358(T) (97.5 %) and Blastobacter aggregatus IFAM 1003(T) (97.2 %). Strain W3(T) formed a monophyletic clade with Blastobacter aggregatus IFAM 1003(T) ( = DSM 1111(T)) in the cluster of species of the genus Rhizobium. Phylogenetic analyses of strain W3(T) using atpD and recA gene sequences confirmed the phylogenetic arrangements obtained by using 16S rRNA gene sequences. Hence, the taxonomic characterization of B. aggregatus DSM 1111(T) was also undertaken. Strains W3(T) and B. aggregatus DSM 1111(T) contained summed feature 8 (18 : 1ω7c and/or 18 : 1ω6c; 65.4 and 70.8 %, respectively) as the major fatty acid, characteristic of the genus Rhizobium. DNA-DNA relatedness of strain W3(T) with Rhizobium selenitireducens LMG 24075(T), Rhizobium daejeonense DSM 17795(T), Rhizobium radiobacter DSM 30147(T) and B. aggregatus DSM 1111(T) was 42, 34, 30 and 34 %, respectively. The DNA G+C contents of strain W3(T) and B. aggregatus DSM 1111(T) were 62.3 and 62.7 mol%, respectively. A nifH gene encoding dinitrogenase reductase was detected in strain W3(T) but not in B. aggregatus DSM 1111(T). Based on the results obtained by phylogenetic and chemotaxonomic analyses, phenotypic characterization and DNA-DNA hybridization, it is concluded that strain W3(T) represents a novel species of the genus Rhizobium, for which the name Rhizobium rosettiformans sp. nov. is proposed (type strain W3(T)  = CCM 7583(T)  = MTCC 9454(T)). It is also proposed that Blastobacter aggregatus Hirsch and Müller 1986 be transferred to the genus Rhizobium as Rhizobium

  4. Identification of reference proteins for Western blot analyses in mouse model systems of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD toxicity.

    Directory of Open Access Journals (Sweden)

    Stephenie D Prokopec

    Full Text Available Western blotting is a well-established, inexpensive and accurate way of measuring protein content. Because of technical variation between wells, normalization is required for valid interpretation of results across multiple samples. Typically this involves the use of one or more endogenous controls to adjust the measured levels of experimental molecules. Although some endogenous controls are widely used, validation is required for each experimental system. This is critical when studying transcriptional-modulators, such as toxicants like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD.To address this issue, we examined hepatic tissue from 192 mice representing 47 unique combinations of strain, sex, Ahr-genotype, TCDD dose and treatment time. We examined 7 candidate reference proteins in each animal and assessed consistency of protein abundance through: 1 TCDD-induced fold-difference in protein content from basal levels, 2 inter- and intra- animal stability, and 3 the ability of each candidate to reduce instability of the other candidates. Univariate analyses identified HPRT as the most stable protein. Multivariate analysis indicated that stability generally increased with the number of proteins used, but gains from using >3 proteins were small. Lastly, by comparing these new data to our previous studies of mRNA controls on the same animals, we were able to show that the ideal mRNA and protein control-genes are distinct, and use of only 2-3 proteins provides strong stability, unlike in mRNA studies in the same cohort, where larger control-gene batteries were needed.

  5. In vitro effects of TCDD, PCB126 and PCB153 on estrogen receptors, caspases and metalloproteinase-2 mRNA expression in the chicken shell gland.

    Science.gov (United States)

    Hrabia, Anna; Leśniak, Agnieszka; Sechman, Andrzej

    2013-01-01

    Among the environmental chemicals which disturb endocrine functions, dioxins and polychlorinated biphenyls (PCBs) are known as the most toxic. Numerous studies in mammals revealed that dioxins and PCBs disrupt functions of the uterus, delay implantation and increase embryo loss. The direct effect of these chemicals on the avian oviduct is not known. Therefore, in the study chicken shell gland tissues were used to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar PCB126 and non-coplanar PCB153 on estrogen receptors (ERs), initiator caspase-1, executioner caspase-3 and metalloproteinase-2 (MMP-2) mRNA expression. Fragments of shell gland tissue isolated from the laying chicken were incubated for 24h with TCDD (100nM), PCB126 (100nM) or PCB153 (100 microM). Quantitative PCR analysis showed that: (1) TCDD increased ER beta (ERbeta) mRNA expression, (2) PCB126 increased ER alpha (ERalpha), ERbeta and caspase-1, and decreased MMP-2 mRNA expression, (3) PCB153 elevated the ERbeta and caspase-1 expression levels and (4) expression of caspase-3 was not altered by any investigated xenobiotics. The results obtained using the shell gland explants model indicate that dioxins and PCBs have a direct effect on the chicken oviduct, especially the shell gland, by affecting the expression of genes involved in the function of this oviductal segment. It is suggested that coplanar PCBs such as PCB126, by changing cellular and extracellular regulators gene expression, may lead to disruption of shell gland activity and impair egg components formed in this organ.

  6. Prenatal Exposure to TCDD Triggers Significant Modulation of microRNA Expression Profile in the Thymus That Affects Consequent Gene Expression

    OpenAIRE

    Singh, Narendra P; Singh, Udai P.; Hongbing Guan; Prakash Nagarkatti; Mitzi Nagarkatti

    2012-01-01

    BACKGROUND: MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to T...

  7. Psychophysical evaluation of the image quality of a dynamic flat-panel digital x-ray image detector using the threshold contrast detail detectability (TCDD) technique

    Science.gov (United States)

    Davies, Andrew G.; Cowen, Arnold R.; Bruijns, Tom J. C.

    1999-05-01

    We are currently in an era of active development of the digital X-ray imaging detectors that will serve the radiological communities in the new millennium. The rigorous comparative physical evaluations of such devices are therefore becoming increasingly important from both the technical and clinical perspectives. The authors have been actively involved in the evaluation of a clinical demonstration version of a flat-panel dynamic digital X-ray image detector (or FDXD). Results of objective physical evaluation of this device have been presented elsewhere at this conference. The imaging performance of FDXD under radiographic exposure conditions have been previously reported, and in this paper a psychophysical evaluation of the FDXD detector operating under continuous fluoroscopic conditions is presented. The evaluation technique employed was the threshold contrast detail detectability (TCDD) technique, which enables image quality to be measured on devices operating in the clinical environment. This approach addresses image quality in the context of both the image acquisition and display processes, and uses human observers to measure performance. The Leeds test objects TO[10] and TO[10+] were used to obtain comparative measurements of performance on the FDXD and two digital spot fluorography (DSF) systems, one utilizing a Plumbicon camera and the other a state of the art CCD camera. Measurements were taken at a range of detector entrance exposure rates, namely 6, 12, 25 and 50 (mu) R/s. In order to facilitate comparisons between the systems, all fluoroscopic image processing such as noise reduction algorithms, were disabled during the experiments. At the highest dose rate FDXD significantly outperformed the DSF comparison systems in the TCDD comparisons. At 25 and 12 (mu) R/s all three-systems performed in an equivalent manner and at the lowest exposure rate FDXD was inferior to the two DSF systems. At standard fluoroscopic exposures, FDXD performed in an equivalent

  8. Methoxychlor suppresses the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 expression in murine Hepa-1c1c7 cells.

    Science.gov (United States)

    Han, Eun Hee; Jeong, Tae Cheon; Jeong, Hye Gwang

    2007-08-01

    Methoxychlor (MXC) is a pesticide that was developed as a replacement for dichlorodiphenyltrichloroethane (DDT). The influence of MXC on CYP1A1 expression or the functions of mouse hepatoma Hepa-1clc7 remain unclear. Cultured Hepa-1c1c7 cells were treated with MXC with or without 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to assess the role of MXC on CYP1A1 expression. MXC alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and MXC in a concentration-dependent manner. Treatment with ICI 182.780, an estrogen-receptor antagonist, did not affect the suppressive effects of MXC on TCDD-inducible EROD activity. TCDD-inducible CYP1A1 mRNA levels were markedly suppressed upon treatment with TCDD and MXC, and this is consistent with their effects on EROD activity. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and an electrophoretic mobility shift assay revealed that MXC reduced the transformation of the aryl hydrocarbons (Ah) receptor to a form capable of specifically binding to the DRE sequence in the promoter region of the CYP1A1 gene. These results suggest that the downregulation of CYP1A1 gene expression by MXC in Hepa-1c1c7 cells might be an antagonism of the DRE binding potential of the nuclear Ah receptor but is not mediated through the estradiol receptor.

  9. Effect of TCDD on telomerase activity of human breast cancer cells%TCDD对乳腺癌细胞端粒酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    吴小琴; 丁国武; 牛静萍; 段蓉; 郭红云; 张晓文

    2008-01-01

    探讨了2,3,7,8-四氯二苯并-ρ-二噁英(TCDD)在体外对雌激素依赖性乳腺癌细胞MCF-7端粒酶活性的影响.用0.5μmol·L-1的2,3,7,8-四氯二苯并-ρ二噁英(TCDD)作用于MCF-7细胞,裂解后提取MCF.7细胞端粒酶.采用BCA方法定量蛋白、重复序列扩增-银染法检测端粒酶活性.结果表明.TCDD作用MCF-7细胞后,细胞端粒酶活性增强,且随作用时间端粒酶活性减弱,但明显高于对照组(P<0.05).结果表明:TCDD有显著增强MCF-7细胞端粒酶活性的作用.

  10. Chemical reaction dynamics of PeCB and TCDD decomposition: A tight-binding quantum chemical molecular dynamics study with first-principles parameterization

    Science.gov (United States)

    Suzuki, Ai; Selvam, Parasuraman; Kusagaya, Tomonori; Takami, Seiichi; Kubo, Momoji; Imamura, Akira; Miyamoto, Akira

    The decomposition reaction dynamics of 2,3,4,4',5-penta-chlorinated biphenyl (2,3,4,4',5-PeCB), 3,3',4,4',5-penta-chlorinated biphenyl (3,3',4,4',5-PeCB), and 2,3,7,8-tetra-chlorinated dibenzo-p-dioxin (2,3,7,8-TCDD) was clarified for the first time at atomic and electronic levels, using our novel tight-binding quantum chemical molecular dynamics method with first-principles parameterization. The calculation speed of our new method is over 5000 times faster than that of the conventional first-principles molecular dynamics method. We confirmed that the structure, energy, and electronic states of the above molecules calculated by our new method are quantitatively consistent with those by first-principles calculations. After the confirmation of our methodology, we investigated the decomposition reaction dynamics of the above molecules and the calculated dynamic behaviors indicate that the oxidation of the 2,3,4,4',5-PeCB, 3,3',4,4',5-PeCB, and 2,3,7,8-TCDD proceeds through an epoxide intermediate, which is in good agreement with the previous experimental reports and consistent with our static density functional theory calculations. These results proved that our new tight-binding quantum chemical molecular dynamics method with first-principles parameterization is an effective tool to clarify the chemical reaction dynamics at reaction temperatures.

  11. Histopathological, Ultrastructural, and Immunohistochemical Assessment of Hippocampus Structures of Rats Exposed to TCDD and High Doses of Tocopherol and Acetylsalicylic Acid

    Directory of Open Access Journals (Sweden)

    Joanna Rosińczuk

    2015-01-01

    Full Text Available The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD on central nervous system consists of changing expression of estrogen receptors, whereas the result of chronic inflammatory reaction caused by dioxin is occurrence of destructive changes in various organs connected with disturbed metabolism of connective tissue and damage of cells. The aim of the study was to determine the effect of dioxins on function, ultrastructure, and cytological and histological structure of hippocampus, particularly on expression of estrogen receptors in central nervous system as well as to define protective influence of tocopherol (TCP and acetylsalicylic acid (ASA on the decrease in activity of proinflammatory effects in central nervous system. It was shown that TCDD contributes to destructive and inflammatory changes along with demyelization of myelin sheaths and atrophy of estrogen receptors in hippocampus. Dioxin contributes to atrophy of estrogen receptors in hippocampus, in which also destructive and inflammatory changes were found along with demyelination of myelin sheaths. Histopathological and ultrastructural image of hippocampus areas in rats, in which both TCP and ASA were used, is characterized by poorly expressed degenerative changes and smaller inflammatory reactivity. Using both TCP and ASA has a protective effect on functions of central nervous system.

  12. ROLES OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-A) IN MEDIATION OF DIOXIN (TCDD)-INDUCED DELAYS IN DEVELOPMENT OF THE MOUSE MAMMARY GLAND

    Science.gov (United States)

    Roles of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a) in Mediation of Dioxin (TCDD)-Induced Delays in Development of the Mouse Mammary Gland.Suzanne E. Fenton, Barbara Abbott, Lamont Bryant, and Angela Buckalew. U.S. EPA, NHEERL, Reproductive Tox...

  13. IMP PCR primers detect single nucleotide polymorphisms for Anopheles gambiae species identification, Mopti and Savanna rDNA types, and resistance to dieldrin in Anopheles arabiensis

    Directory of Open Access Journals (Sweden)

    Howell Paul I

    2006-12-01

    Full Text Available Abstract Background Polymerase chain reactions to distinguish single-nucleotide polymorphisms are commonly used for mosquito identification and identifying insecticide resistance alleles. However, the existing methods used for primer design often result in analyses that are not robust or require additional steps. Methods Utilizing oligonucleotides that are unique in having an intentional mismatch to both templates three bases from the SNP at the 3-prime end, three new PCR assays that distinguish SNP targets using standard gel electrophoresis of undigested DNA fragments were developed and tested. These were applied to: (1 an alternative ribosomal DNA PCR assay to distinguish five members of the Anopheles gambiae complex; (2 detection of the Mopti and Savanna rDNA types; and (3 an assay to distinguish resistance to dieldrin (Rdl alleles in Anopheles arabiensis. Results Reproducible specific amplification of the target alleles was observed in all three assays. The results were consistent with existing analyses but proved simpler and the results more distinct in our hands. Conclusion The simplicity and effectiveness of the method should be utilized in these and other PCR analyses to increase their specificity and simplicity. These results have the potential to be extended not only to mosquito analyses but also to parasite and human polymorphisms.

  14. IMP PCR primers detect single nucleotide polymorphisms for Anopheles gambiae species identification, Mopti and Savanna rDNA types, and resistance to dieldrin in Anopheles arabiensis.

    Science.gov (United States)

    Wilkins, Elien E; Howell, Paul I; Benedict, Mark Q

    2006-12-19

    Polymerase chain reactions to distinguish single-nucleotide polymorphisms are commonly used for mosquito identification and identifying insecticide resistance alleles. However, the existing methods used for primer design often result in analyses that are not robust or require additional steps. Utilizing oligonucleotides that are unique in having an intentional mismatch to both templates three bases from the SNP at the 3-prime end, three new PCR assays that distinguish SNP targets using standard gel electrophoresis of undigested DNA fragments were developed and tested. These were applied to: (1) an alternative ribosomal DNA PCR assay to distinguish five members of the Anopheles gambiae complex; (2) detection of the Mopti and Savanna rDNA types; and (3) an assay to distinguish resistance to dieldrin (Rdl) alleles in Anopheles arabiensis. Reproducible specific amplification of the target alleles was observed in all three assays. The results were consistent with existing analyses but proved simpler and the results more distinct in our hands. The simplicity and effectiveness of the method should be utilized in these and other PCR analyses to increase their specificity and simplicity. These results have the potential to be extended not only to mosquito analyses but also to parasite and human polymorphisms.

  15. Deformities, PCBs, and TCDD-equivalents in double-crested cormorants (Phalacrocorax auritus) and Caspian terns (Hydroprogne caspia) of the Upper Great Lakes 1986–1991: Testing a cause-effect hypothesis

    Science.gov (United States)

    Ludwig, James P.; Kurita-Matsuba, Hiroko; Auman, Heidi J.; Ludwig, Matthew E.; Summer, Cheryl L.; Giesy, John P.; Tillitt, Donald E.; Jones, Paul D.

    1996-01-01

    Deformities have been reported in many species of colonial waterbirds from several localities on the Laurentian Great Lakes. The hypothesis that deformities were caused by either polychlorinated biphenyls (PCBs) or contaminants measured as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQs) is tested in this review of available data on concentrations of contaminants in eggs and observed deformities in embryos and chicks of double-crested cormorants (Phalacrocorax auritus) and Caspian terns (Hydroprogne caspia) between 1986 and 1991. Hatched chicks, live and dead eggs retrieved from 37 colonies in the upper Great Lakes were assessed for gross anatomical deformities. Rates of embryo death from seven regions of the upper Great Lakes were measured annually between 1986–1991. Half the embryos found dead in eggs were deformed. Nineteen types of abnormalities or deformities were observed. Subcutaneous edema in cormorants and gastroschisis in terns were the most common abnormalities in live or dead eggs. One of ten crossed-billed cormorant embryos survived to hatch. No bill-deformed terns hatched, although tern embryos had a greater rate of crossed-bills than cormorants. The suite of deformities and abnormalities found was similar to that produced in chickens by exposure to planar polychlorinated biphenyl (pPCB) and dioxin congeners. Hatching and deformity rates were correlated with concentrations ofpPCBs and TCDD-EQs. Planar PCB congeners that contributed most of the TCDD-EQs were present at concentrations sufficient to cause the observed effects. TCDD-EQs measured by H4IIE rat hepatoma cell 7-ethoxyresorufin O-deethylase (EROD) bioassay were highly correlated with deformity rates observed in cormorant chicks, live and dead eggs, and egg death rates. Similar correlations of TCDD-EQs with deformity rates were found in hatched tern chicks, dead eggs, and egg death rates, but not in live eggs. TCDD-EQs were more highly correlated to deformity and embryo death rates

  16. Combination effects of nano-TiO2 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on biotransformation gene expression in the liver of European sea bass Dicentrarchus labrax.

    Science.gov (United States)

    Vannuccini, Maria Luisa; Grassi, Giacomo; Leaver, Michael J; Corsi, Ilaria

    2015-01-01

    The aim of present study was to investigate the influence of titanium dioxide nanoparticles (nano-TiO2, Aeroxide® P25) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) dependent biotransformation gene expression in liver of juvenile European sea bass Dicentrarchus labrax. An in vivo 7day waterborne exposure was performed with nano-TiO2 (1mg/L) and 2,3,7,8-TCDD (46pg/L), singly and in combination. The mRNA expression of aryl hydrocarbon receptor repressor (Ahrr), estrogen receptor (erβ2), ABC transport proteins as Abcb1, Abcc1-c2-g2, cytochrome P450 (cyp1a), glutathione-s-transferase (gsta), glutathione reductase (gr) and engulfment and motility (ELMO) domain-containing protein 2 (elmod2) was investigated. Ahrr, erβ2, abcc1 and abcg2 resulted down-regulated with respect to controls in all experimental groups. Co-exposure to nano-TiO2 and 2,3,7,8-TCDD caused a further significant down regulation of ahrr, erβ2, Abcb1 and Abcc2 compared to single chemical exposure (nano-TiO2 or 2,3,7,8-TCDD alone). No effects were observed for 2,3,7,8-TCDD and nano-TiO2 alone in abcb1 gene, while abcc2 was down-regulated by nano-TiO2 alone. Cyp1a, gst and elmod2 genes were up-regulated by 2,3,7,8-TCDD and to a similar extent after co-exposure. Overall the results indicate that nano-TiO2 is unlikely to interfere with 2,3,7,8-TCDD-dependent biotransformation gene expression in the liver of European sea bass, although the effects of co-exposure observed in ABC transport mRNAs might suggest an impact on xenobiotic metabolite disposition and transport in European sea bass liver.

  17. Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands

    Directory of Open Access Journals (Sweden)

    Vezina Chad M

    2010-10-01

    Full Text Available Abstract Background Two year cancer bioassays conducted by the National Toxicology Program have shown chronic exposure to dioxin-like compounds (DLCs to lead to the development of both neoplastic and non-neoplastic lesions in the hepatic tissue of female Sprague Dawley rats. Most, if not all, of the hepatotoxic effects induced by DLC's are believed to involve the binding and activation of the transcription factor, the aryl hydrocarbon receptor (AhR. Toxicogenomics was implemented to identify genomic responses that may be contributing to the development of hepatotoxicity in rats. Results Through comparative analysis of time-course microarray data, unique hepatic gene expression signatures were identified for the DLCs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD (100 ng/kg/day and 3,3',4,4',5-pentachlorobiphenyl (PCB126 (1000 ng/kg/day and the non-DLC 2,2',4,4',5,5',-hexachlorobiphenyl (PCB153 (1000 μg/kg/day. A common time independent signature of 41 AhR genomic biomarkers was identified which exhibited at least a 2-fold change in expression following subchronic (13-wk and chronic (52-wk p.o. exposure to TCDD and PCB126, but not the non DLC, PCB153. Real time qPCR analysis validated that 30 of these genes also exhibited at least a 2-fold change in hepatic expression at 24 hr following a single exposure to TCDD (5 μg/kg, po. Phenotypic anchoring was conducted which identified forty-six genes that were differently expressed both following chronic p.o. exposure to DLCs and in previously reported studies of cholangiocarcinoma or hepatocellular adenoma. Conclusions Together these analyses provide a comprehensive description of the genomic responses which occur in rat hepatic tissue with exposure to AhR ligands and will help to isolate those genomic responses which are contributing to the hepatotoxicity observed with exposure to DLCs. In addition, the time independent gene expression signature of the AhR ligands may assist in identifying other agents

  18. Non-additive hepatic gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) co-treatment in C57BL/6 mice

    OpenAIRE

    Kopec, Anna K; Souza, Michelle L. D.; Mets, Bryan D.; Burgoon, Lyle D; Reese, Sarah E; Archer, Kellie J; Potter, Dave; Tashiro, Colleen; Sharratt, Bonnie; Harkema, Jack R.; Zacharewski, Timothy R

    2011-01-01

    Interactions between environmental contaminants can lead to non-additive effects that may affect the toxicity and risk assessment of a mixture. Comprehensive time course and dose-response studies with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), non-dioxin-like 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) and their mixture were performed in immature, ovariectomized C57BL/6 mice. Mice were gavaged once with 30 μg/kg TCDD, 300 mg/kg PCB153, a mixture of 30 μg/kg TCDD with 300 mg/kg PCB153 (MIX) or...

  19. Uncertainty analysis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cancer dose-response for three occupational cohorts.

    Science.gov (United States)

    Dong, Zhaomin; Yuan, Guanxiang; Hu, Jianying

    2016-03-01

    While the U.S. EPA has issued a draft report with a 1% TCDD effective dose (ED01) of 87.9pg/kg/day based on continuous integration of key scientific evidence, a detailed and comprehensive uncertainty analysis has not been well documented. In this study, a new estimate for ED01 was derived based on uncertainty analysis by quantitatively assessing the potential bias arising from the selection of kinetic models, dose-response models and cohorts. The cumulative serum lipid concentration (CSLC) and cumulative body burden (CBB) were reconstructed as dose metrics using a concentration- and age-dependent pharmacokinetic model (CADM), physiologically based pharmacokinetic model (PBPK), and age-dependent half-life model (FV), and the reconstructed dose metrics based on CADM and PBPK were generally higher than those based on the FV model. Three dose-response curves (linear, multiplicative and power) were used to link dose metrics and cancer risk to estimate ED01, and the linear model resulted in the lowest ED01, followed by the power model and multiplicative model, for the same cohort. Meanwhile, ED01 based on the CADM model was the highest, followed by those based on the PBPK model and first-order model. Finally, the ED01 was estimated to be 17.03±7.83pg/kg/day by statistically analyzing the distribution of ED01 values based on various kinetic models, cohorts and dose-response models. The study presented here strengthens the scientific basis for understanding the potential health implications of TCDD exposure.

  20. The legacy pesticide dieldrin acts as a teratogen and alters the expression of dopamine transporter and dopamine receptor 2a in zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Sarty, Kathleena I; Cowie, Andrew; Martyniuk, Christopher J

    2017-04-01

    Dieldrin (DLD) is a lipophilic pesticide that shows environmental persistence. The objectives were to determine the effects of DLD on GABAergic and dopaminergic systems in developing zebrafish. Both chorionated and dechorionated embryos (~24h post-hatch) were exposed to a single concentration of DLD (0.347-3470μM) for 48h. Following exposure, a subset of larvae was placed into clean water for 6days (i.e. depuration phase). Chorionated embryos showed 30%), suggesting that the chorion protected the embryos. Over a 6day depuration phase, there was a dose dependent effect observed in both the "dechorionated and chorionated embryo" treatments for larval mortality (>60%). At the end of depuration, there was no detectable change in neuro-morphological endpoints that included the ratio of notochord length to body length (%) and the ratio of head area to body area (%). However, DLD did induce cardiac edema, skeletal deformities, and tremors. GABA-related transcripts were not affected in abundance by DLD. Conversely, the relative mRNA levels of dopamine transporter (dat1) and dopamine receptor drd2a mRNA were decreased in dechorionated, but not chorionated, embryos. These data suggest that DLD can alter the expression of transcripts related to dopaminergic signaling. Lastly, GABAA receptor subunits gabrB1 and gabrB2, as well as dopamine receptors drd1 and drd2a, were inherently higher in abundance in dechorionated embryos compared to chorionated embryos. This is an important consideration when incorporating transcriptomics into embryo testing as expression levels can change with removal of the chorion prior to exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD in Han/Wistar and Long–Evans rats with different aryl hydrocarbon receptor (AhR structures

    Directory of Open Access Journals (Sweden)

    Sabrina B. Sholts

    2015-01-01

    Full Text Available Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W and dioxin-sensitive Long–Evans (L–E rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM and dose–response modeling. The strongest effects were shown by L–E and H/W rats with daily exposures of 100 and 1000 ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs for cranial size reduction in L–E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L–E rats, respectively, most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L–E rats had vaults and bases of comparable size, the face was 6.4% larger in L–E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on

  2. Effects of the environmental contaminants DEHP and TCDD on estradiol synthesis and aryl hydrocarbon receptor and peroxisome proliferator-activated receptor signalling in the human granulosa cell line KGN.

    Science.gov (United States)

    Ernst, Jana; Jann, Johann-Christoph; Biemann, Ronald; Koch, Holger M; Fischer, Bernd

    2014-09-01

    Environmental contaminants binding to transcription factors, such as the aryl hydrocarbon receptor (AhR) and the alpha and gamma peroxisome proliferator-activated receptors (PPARs), contribute to adverse effects on the reproductive system. Expressing both the AhR and PPARs, the human granulosa cell line KGN offers the opportunity to investigate the regulatory mechanisms involved in receptor crosstalk, independent of overriding hormonal control. The aim of the present study was to investigate the impact of two environmental contaminants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an AhR ligand) and di-(2-ethylhexyl) phthalate (DEHP, a PPAR ligand), on gonadotrophin sensitivity and estrogen synthesis in KGN cells. Accumulation of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in DEHP-exposed cells was measured by high-performance liquid chromatography mass spectrometry, thereby demonstrating DEHP metabolism to MEHP by KGN cells. By employing TCDD ( an AhR agonist), rosiglitazone (a PPARgamma agonist) or bezafibrate (a PPARalpha agonist), the presence of a functional AhR and PPAR cascade was confirmed in KGN cells. Cytotoxicity testing revealed no effect on KGN cell proliferation for the concentrations of TCDD and DEHP used in the current study. FSH-stimulated cells were exposed to TCDD, DEHP or a mix of both and estradiol synthesis was measured by enzyme-linked immunosorbent assay and gene expression by quantitative RT-PCR. Exposure decreased estradiol synthesis (TCDD, DEHP, mix) and reduced the mRNA expression of CYP19 aromatase (DEHP, mix) and FSHR (DEHP). DEHP induced the expression of the alpha and gamma PPARs and AhR, an effect which was inhibited by selective PPAR antagonists. Studies in the human granulosa cell line KGN show that the action of endocrine-disrupting chemicals may be due to a direct activation of AhR, for example by TCDD, and by a transactivation via PPARs, for example by DEHP, inducing subsequent transcriptional changes with a broad

  3. Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153.

    Science.gov (United States)

    van Esterik, J C J; Verharen, H W; Hodemaekers, H M; Gremmer, E R; Nagarajah, B; Kamstra, J H; Dollé, M E T; Legler, J; van der Ven, L T M

    2015-12-01

    Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10-10,000 pg/kg body weight/day; PCB 153: 0.09-1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes.

  4. Design and fabrication of molecularly imprinted polymer-based potentiometric sensor from the surface modified multiwalled carbon nanotube for the determination of lindane (γ-hexachlorocyclohexane), an organochlorine pesticide.

    Science.gov (United States)

    Anirudhan, Thayyath S; Alexander, Sheeba

    2015-02-15

    A novel potentiometric sensor with high selectivity in addition to sensitivity was developed for the determination of lindane, γ-hexachlorocyclohexane (γ-HCCH), based on the modification of γ-HCCH imprinted polymer film onto the surface of Cu electrode. A multiwalled carbon nanotube (MWCNT) was grafted using glycidyl methacrylate (GMA). The reaction of MWCNT with GMA produces MWCNT-g-GMA and the epoxide ring present in the GMA upon reaction with allylamine produces the vinylated MWCNT (MWCNT-CH = CH2). MWCNT based imprinted polymer (MWCNT-MIP) was synthesized by means of methacrylic acid (MAA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross linker, α,α'-azobisisobutyronitrile (AIBN) as the initiator and γ-HCCH, an organochlorine pesticide molecule, as the template. The optimizations of operational parameters were also done. Organized material was characterized by means of FTIR, XRD, Raman spectra and TEM analyses. The sensor responds to γ-HCCH in the range 1 × 10(-10)-1 × 10(-3)M and the detection limit was found to be 1.0 × 10(-10)M.

  5. Relative Bioavailability of a- and b-hexachlorocyclohexane in various soils from a Contaminated Site - See more at: http://sciencebeingjournal.com/past.html/4#sthash.KMP2scTj.dpuf

    Directory of Open Access Journals (Sweden)

    Ashish Srivastava,

    2014-06-01

    Full Text Available Bioavailability of α- and β-isomers of a chlorinated insecticide hexachlorocyclohexane (HCH in several field soils that were contaminated for different time periods was evaluated. Results revealed that the availability of α-HCH to the degradative microorganisms was 75-80% in all the soils, but considerable differences in the availability of β-HCH in different soils were observed. Thus, 80-90% β-HCH was available to ‘E.coli-LinB’ cells from a freshly spiked soil, and ~70, 60 and 45% from soils that were contaminated for short-, medium- and long-term, respectively. Similarly, their amounts extracted by 50 mM hydroxypropyl-β-cyclodextrin also showed the same trend. It suggests that the bioavailability of β-HCH decreases progressively with an increase in the age of contamination, but of α-HCH is not affected under the same conditions. Reasons behind this differential availability are discussed. Results are important for correct risk-assessment of these residues in the contaminated soils.

  6. In vivo – in vitro toxicogenomic comparison of TCDD-elicited gene expression in Hepa1c1c7 mouse hepatoma cells and C57BL/6 hepatic tissue

    Directory of Open Access Journals (Sweden)

    Boverhof Darrell R

    2006-04-01

    Full Text Available Abstract Background In vitro systems have inherent limitations in their ability to model whole organism gene responses, which must be identified and appropriately considered when developing predictive biomarkers of in vivo toxicity. Systematic comparison of in vitro and in vivo temporal gene expression profiles were conducted to assess the ability of Hepa1c1c7 mouse hepatoma cells to model hepatic responses in C57BL/6 mice following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Results Gene expression analysis and functional gene annotation indicate that Hepa1c1c7 cells appropriately modeled the induction of xenobiotic metabolism genes in vivo. However, responses associated with cell cycle progression and proliferation were unique to Hepa1c1c7 cells, consistent with the cell cycle arrest effects of TCDD on rapidly dividing cells. In contrast, lipid metabolism and immune responses, representative of whole organism effects in vivo, were not replicated in Hepa1c1c7 cells. Conclusion These results identified inherent differences in TCDD-mediated gene expression responses between these models and highlighted the limitations of in vitro systems in modeling whole organism responses, and additionally identified potential predictive biomarkers of toxicity.

  7. TCDD诱发昆明小鼠腭突畸形过程中对 Jagged2蛋白表达的影响%Effects of TCDD on expression of Jagged2 during the induction of mouse cleft palate

    Institute of Scientific and Technical Information of China (English)

    宋敏; 张艳萍; 张丽红; 牟瑞丽

    2015-01-01

    目的::检测四氯二苯并二恶英( TCDD )诱发昆明小鼠腭裂畸形过程中对Jagged2蛋白表达的影响。方法:将30只昆明孕鼠随机分为实验组和对照组,实验组GD12天孕鼠一次性灌服40μg/kg TCDD,对照组灌服等剂量花生油,分别于GD13、GD14、GD15剖腹取胎鼠头部标本,作冠状位组织切片。采用免疫组化方法检测胚胎腭中Jag-ged2蛋白表达。结果:Jagged2主要表达于胚胎腭突上皮组织;GD14、GD15时,对照组中Jagged2蛋白表达显著下降( P<0.05),但实验组未出现明显表达变化。结论:Jagged2在胚胎腭突上皮的异常表达可能参与了TCDD诱发小鼠腭裂畸形发生。%Objective:To explore the effects of TCDD on Jagged2 expression during the induction of the mouse cleft palate. Methods:Thirty pregnant Kunming mice were randomly di-vided into experimental and control groups. The experimental group was given TCDD ( 40μg/kg) by gavage on gestational day 12(GD12),and the control group was given the same dose of peanut oil. Fetuses were removed out on GD13,GD14 and GD15. The heads were sliced in coro-nal plane. The expression of Jagged2 in embryonic palate was determined by immunohistochem-istry. Results:The expression of Jagged2 was detected in the palate epithelium in both groups on GD13,and its expression was obviously down-regulated on GD14 and GD15(P<0. 05) in the control group. Meanwhile,no significant reduction was observed in experimental group. Con-clusion:The abnormal persistent high expression of Jagged2 in palate epithelium may be related with the cleft palate induced by TCDD in mice.

  8. NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (Gavage Studies).

    Science.gov (United States)

    2006-04-01

    DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized, they accumulate in body tissue, mainly adipose, resulting in chronic lifetime human exposure. Since human exposure to DLCs always involves a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. TCDD is not manufactured commercially other than for scientific research purposes. The main sources of TCDD releases into the environment are from combustion and incineration; metal smelting, refining, and processing; chemical

  9. 四氯二苯并二恶英与妇科疾病%Research Progress of Correlation Between TCDD and Gynecological Diseases

    Institute of Scientific and Technical Information of China (English)

    张丽君

    2011-01-01

    四氯二苯并二恶英(tetrachlorodibenzodioxin,TCDD)是毒性最大的化合物之一,可损伤多种脏器功能并具有免疫抑制和致癌作用.TCDD可导致多种妇科疾病,如子宫内膜异位症、卵巢癌和卵巢功能早衰等,并在一定程度上促进这些疾病的发展.然而,据流行病学调查发现,暴露在TCDD中却使另外一种妇科疾病--子宫肌瘤的发病率降低.因此,研究TCDD与妇科常见病的关系可进一步认识TCDD的特性及作用机制,并为预防这些疾病提供帮助.

  10. Expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1) and CYP1 family monooxygenase mRNAs and their activity in chicken ovarian follicles following in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Antos, Piotr A; Błachuta, Małgorzata; Hrabia, Anna; Grzegorzewska, Agnieszka K; Sechman, Andrzej

    2015-09-02

    The aim of this in vitro study was to determine the effect of TCDD and luteinizing hormone (LH) on mRNA expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1), and the CYP1 family monooxygenases (CYP1A4, CYP1A5, CYP1B1), and to assess the basal and TCDD-induced activity of these enzymes in chicken ovarian follicles. White (WF) and yellowish (YF) prehierarchical follicles and fragments of the theca (TL) and granulosa (GL) layers of the 3 largest preovulatory follicles (F3-F1) were exposed to TCDD (10nM), ovine LH (oLH; 10ng/mL) or a combination of TCDD (10nM) and oLH (10ng/mL), and increasing doses of TCDD (0.01-100nM). AHR1 and ARNT1 mRNA transcripts were found in all examined follicles. The effect of TCDD and oLH on AHR1 and ARNT1 mRNA expression depended on the maturational state of the follicle. CYP1A4 was predominantly expressed in the GL of the F3-F1 follicles; in comparison with the WF, a higher level of CYP1A5 mRNA was found both in the GL and TL of F3-F1 follicles. Alternatively, the highest level of CYP1B1 mRNA was noticed in the WF follicles. In different developmental stages of the follicle TCDD and oLH induced a different CYP1 isoform. TCDD increased EROD and MROD activities in all the investigated ovarian follicles. In conclusion, AHR1 and ARNT1 mRNA expression indicate that the chicken ovary is a target tissue for dioxin and dioxin-like compounds. The expression of CYP1-family genes and TCDD-inducible EROD and MROD activities in ovarian follicles suggest the possibility of xenobiotic detoxification in the chicken ovary.

  11. TCDD Protects the Mouse Kidneys against Ischemia-reperfusion Injury by Activating the Aryl Hydrocarbon Receptor%TCDD激活芳香烃受体减轻小鼠肾脏缺血再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    蔡兰军; 余道武; 高义; 杨超; 周鸿敏; 陈忠华

    2013-01-01

    Objective To investigate the protective effects of 2 ,3 ,7 ,8-tetrachlorodibenzo-p-dioxin (TCDD) on ischemia-reperfusion injury (IRI) of the kidneys in mice and the possible mechanism. Methods Kidney IRI models were established in C57BL/6 (H-2b) mice. Animals were divided into TCDD-treated group (0. 5 μg TCDD intraperitoneally given to a mouse 24 h before operation) ,PBS control group (200 μL PBS intraperitoneally administered to a mouse 24 h before operation) ,sham group and normal group. The life time of the animals was recorded ,and the kidney function [blood urea nitrogen (BUN ) and serum creatinine (Scr)]measured. Morphologic changes of the IRI kidney were evaluated by light microscopy. The effect of TCDD on the differentiation of naive T cells into regulatory T cells (Treg cells) was observed invitro. The phenotype of T cells in the peripheral blood or spleens of IRI models was measured by flow cytometry. Results The life time was significantly prolonged and the kidney function improved in the TCDD-treated group as compared with those in the PBS control group (P<0. 05 ). The pathological changes of the kidney in TCDD-treated group were significantly alleviated when compared with those in PBS con -trol group. TCDD selectively expanded the subgroup of CD4+ CD25+ Foxp3+ regulatory T cells invitro (P<0. 05 ) ,as well as Treg cells in the peripheral blood and spleens of IRI models in vivo (P<0. 05). Conclusion Activation of the arly hydrocarbon receptor (AHR) by TCDD could obviously improve the kidney function of IRI models ,which may be associated with the expansion of the Treg cell subgroup.%目的 论证2,3,7,8-四氯联苯对二恶英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)激活芳香烃受体(aryl hydrocarbon receptor,AHR)在小鼠肾脏缺血再灌注损伤(ischemia-reperfusion injury,IRI)中的保护作用并探讨其机制.方法 建立C57BL/6小鼠肾脏缺血再灌注损伤模型,设TCDD治疗组(术前24 h腹腔注射TCDD 0.5 μg /

  12. Effects of lactational exposure to organochlorine pesticides, PCBs and dioxins on immune response and thyroid hormone systems in Japanese male and female infants

    Energy Technology Data Exchange (ETDEWEB)

    Nagayama, J. [School of Health Sciences, Kyushu Univ., Fukuoka (Japan); Tsuji, H. [Kitakyushu-Tsuyazaki Hospital, Fukuoka (Japan); Iida, T.; Nakagawa, R.; Matsueda, T.; Hirakawa, H. [Fukuoka Inst. of Health and Environmental Sciences, Fukuoka (Japan); Shiraha, A.; Yanagawa, T. [Graduate School of Mathematics, Kyushu Univ., Fukuoka (Japan); Fukushige, J. [Fukuoka Children' s Hospital, Fukuoka (Japan); Watanabe, T. [Watanabe O.B.G.Y. Clinic, Fukuoka (Japan)

    2004-09-15

    Our environments including food have been polluted with some organochlorine compounds such as dioxins, polychlorinated biphenyls (PCBs) and pesticides. Japanese people have also been contaminated with these chemicals. Consequently, some pesticides such as hexachlorocyclohexans (HCHs), 1,1,1-trichloro- 2,2-bis-(4-chlorophenyl)-ethane (DDT), dieldrin and heptachlor epoxide (HCE), and PCBs have been determined in Japanese breast milk and their mean or median concentrations on fat weight basis were about 420, 330, 3, 4 and 110 ppb, respectively. Their levels were considered more than 100 to 10,000 times higher than those of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs), so-called dioxins, in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent (TEQ) value as a whole. Therefore, we should give due attention to possible health consequences of these organochlorine pesticides and PCBs as well as dioxins in Japanese infants. We have already reported effects of the perinatal exposure to these compounds on lymphocyte subsets and thyroid hormone statuses in the peripheral blood of Japanese infants. In this study, in order to clarify the sexual distinction in their effects on the immune response and thyroid hormone systems, we investigated the lymphocyte subsets and thyroid related chemicals in the blood of Japanese male and female infants in relation to their concentrations of the breast milk.

  13. TCDD诱导软骨细胞细胞凋亡的研究%Studies On The Toxicity of TCDD on Apoptosis in Chondrocyte

    Institute of Scientific and Technical Information of China (English)

    赵玉红; 吴丽霞; 赵玉岩; 郭磊

    2007-01-01

    目的:探讨不同浓度的TCDD对体外培养软骨细胞程序性死亡过程的影响.方法:胰酶消化法体外培养兔的软骨细胞;软骨细胞株暴露于二(噁)英(TCDD)24 h(浓度为1×10-10~1×10-8mol/L);光镜和透射电镜观察软骨细胞株细胞形态变化;流式细胞仪检测软骨细胞株细胞凋亡率.结果:1×10-10~1×10-8mol/L的TCDD诱导软骨细胞出现核固缩、碎裂和凋亡小体,并随TCDD浓度的增加而更明显;TCDD诱导的软骨细胞凋亡呈剂量依赖效应,1×10-10~1×10-8mol/L浓度的TCDD作用24 h后,软骨细胞株凋亡率分别为11.75%±2.41%,19.5%±2.75%,27.5%±3.45%,对照组为5.21%±2.46%,差异有显著性(P<0.05).结论:TCDD可以诱导体外培养的软骨细胞发生细胞凋亡.

  14. EFFECTS OF TEA POLYPHENOLS ON LIVER DAMAGE CAUSED BY TCDD AND ITS POSSIBLE MECHANISM%茶多酚对二恶英所致肝损的作用及机理研究

    Institute of Scientific and Technical Information of China (English)

    刘燕群; 谭佑铭; 沈红兵; 周宜开

    2008-01-01

    [目的]研究茶多酚(TP)对二恶英(TCDD)所致肝损毒作用的保护作用及可能机理.[方法]实验分为5组:对照组;TCDD组(终浓度20nmol/L);TP低、中、高剂量组.TP组(20nmol/L TCDD+终浓度分别为5、10、25mg/L的茶多酚).分别给药处理后,测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的活性.[结果]与TCDD组相比,5mg/L和10mg/L TP使细胞的生存率由59.74%上升到65.5%和80.0%,给予TCDD后SOD、 GSH-Px活性降低与对照组比较差异有统计学意义;TCDD+低、中剂量TP组SOD及GSH-Px值高于TCDD组(P<0.05),而MDA的含量降低;但TP剂量(25mg/L)再增加时其拮抗作用不明显.[结论]Tp在一定程度上缓解TCDD所致的肝损伤,其可能机制可能与抗氧化功能有关.

  15. The Effects of TCDD on Pregnant Cynomolgus Macaque (MacacaFascicularis) and its Pregnancy Outcome%TCDD对猕猴妊娠期及其妊娠结局的毒性影响

    Institute of Scientific and Technical Information of China (English)

    郭玉梅; Lasley,B

    2000-01-01

    在雌猴妊娠第12天采用灌胃法一次性给予TCDD,剂量为1.0、2.0、4.0μg/kg.bw,每个剂量组4个动物。对照组(7个动物)给予相同体积的溶媒(丙酮-色拉油)。结果发现母猴在染毒10天后相继出现食欲下降、体重降低、脱毛、皮炎和贫血等中毒症状,染毒组12只猴子有10只在怀孕的第22到32天发生早期胚胎丢失。结果表明,低剂量TCDD可导致妊娠期猕猴出现中毒症状,并影响妊娠结局。%Females macaques were administrated single doses of 1, 2,4pg/kg TCDD(n = 4 per dose group)on gestational day (GD)12.The controls(n = 7)received the same dosing volume of acetone-coin oil. The results showed that poor appetite, weight loss, alope-cia, dermatitis, anemia and other toxic reactions were recordedsince rtrteatment day 10, and early fetal loss occurred between GDs22 and 32 in 10 of the 12 animals treated, with TCDD. The resultsdemonstrated that toxicity was induced by low level TCDD inpregnant macaques and pregnancy outcomes were affected too.

  16. Observation of Ultrastructure and Morphous of Mouse Embryonic Palate Interfered by TCDD and Vitamin B6.%TCDD和B6联合作用下小鼠腭板形态的扫描电镜观察

    Institute of Scientific and Technical Information of China (English)

    李承浩; 石冰; 何苇; 蒙田; 卢胜军

    2010-01-01

    目的:二恶英(TCDD)和维生素B6联合作用下小鼠腭板形态的扫描电镜观察.方法:对孕期10 d(GD10)的小鼠,分别胃饲TCDD 24 μg/kg,5 mg、10 mg、20 mg B6/kg+TCDD 24 μg/kg,对照组胃饲芝麻油50 ml/kg,然后分别在GD12.5、GD13.5、GD14.5、GD15.5和GD17.5处死孕鼠,检查GD17.5胎鼠有无腭裂的发生,GD12.5、GD13.5、GD14.5、GD15.5胎鼠用于扫描电镜观察.结果:TCDD组的腭裂发生率为55.56%,对照组未见腭裂发生,TCDD+B6组浓度梯度下腭裂发生率为31.81%(5 mg),44.44%(10 mg),40.90%(20 mg).扫描电镜对照组腭中嵴上皮细胞形态规整,有大量微丝,伪足,随着孕期增加,融合的进行,微丝,伪足逐渐消失.TCDD组细胞肿胀变形,表面光滑,未见微丝,和伪足,而且形态并不随孕期的延长而改变,B6组腭中嵴上皮完全消失和TCDD组类似.结论:维生素B6不能恢复小鼠腭中嵴上皮细胞的表面超微结构,从而无法逆转TCDD导致腭裂效应.

  17. Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague-Dawley rats.

    Science.gov (United States)

    Hooth, Michelle J; Nyska, Abraham; Fomby, Laurene M; Vasconcelos, Daphne Y; Vallant, Molly; DeVito, Michael J; Walker, Nigel J

    2012-11-15

    In this study we assessed the relative toxicity and potency of the chlorinated naphthalenes 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) and 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemicals were administered in corn oil:acetone (99:1) by gavage to female Harlan Sprague-Dawley rats at dosages of 0 (vehicle), 500, 1500, 5000, 50,000 and 500,000 ng/kg (PCN 66 and PCN 67) and 1, 3, 10, 100, and 300 ng/kg (TCDD) for 2 weeks. Histopathologic changes were observed in the thymus, liver and lung of TCDD treated animals and in the liver and thymus of PCN treated animals. Significant increases in CYP1A1 and CYP1A2 associated enzyme activity were observed in all animals exposed to TCDD, PCN 66 and PCN 67. Dose response modeling of CYP1A1, CYP1A2 and thymic atrophy gave ranges of estimated relative potencies, as compared to TCDD, of 0.0015-0.0072, for PCN 66 and 0.00029-0.00067 for PCN 67. Given that PCN 66 and PCN 67 exposure resulted in biochemical and histopathologic changes similar to that seen with TCDD, this suggests that they should be included in the WHO toxic equivalency factor (TEF) scheme, although the estimated relative potencies indicate that these hexachlorinated naphthalenes should not contribute greatly to the overall human body burden of dioxin-like activity.

  18. Effects of three drugs on mouse embryonic palate ultrastructure after feeding TCDD%3种药物对饲服TCDD的胎鼠腭突超微结构的影响

    Institute of Scientific and Technical Information of China (English)

    何晓梦; 刘翠苹; 袁心刚; 魏光辉; 傅跃先

    2014-01-01

    目的:观察叶酸、白藜芦醇和α-萘黄酮拮抗四氯二苯二(口恶)英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)诱导胎鼠腭裂发生的效应,及对饲服TCDD的胎鼠腭突表面超微结构的影响.方法:妊娠第10天(gestation day 10,GD10)孕鼠随机分组,每组8只.TCDD组以TCDD 28μg/kg灌胃,对照组以玉米油0.1 ml灌胃,叶酸组以叶酸10 mg/kg+ TCDD 28 μg/kg灌胃、白藜芦醇组以白藜芦醇50 mg/kg+TCDD 28 μg/kg灌胃、α-萘黄酮组以α-萘黄酮5 mg/kg+TCDD 28 μg/kg灌胃,于GD17.5在解剖显微镜下观察胎鼠腭裂的发生率.另取15只孕鼠随机分组,每组3只,处理方法同前,分别于GD13.5、14.5、15.5剪取胎鼠头部,扫描电镜观察腭突表面的超微结构.结果:TCDD组胎鼠腭裂发生率为92.86%,对照组未见胎鼠腭裂形成.叶酸组、白藜芦醇组和α-萘黄酮组胎鼠腭裂发生率分别为73.08%、74.51%、65.52%,与TCDD组相比,差异有统计学意义(P<0.05).TCDD组腭中嵴上皮细胞表面逐渐破裂、皱缩,伪足结构逐渐减少、消失,最终形成腭裂;对照组、叶酸组、白藜芦醇组和α-萘黄酮组腭中嵴上皮细胞表面光滑整齐、饱满膨胀,表面丝状伪足逐渐增多、延长,一直持续到腭突融合结束.结论:叶酸、白藜芦醇和α-萘黄酮均能恢复小鼠腭中嵴上皮细胞表面的超微结构,从而拮抗TCDD的致腭裂效应.

  19. Do marine bacteria degrade. alpha. -hexachlorocyclohexane stereoselectively

    Energy Technology Data Exchange (ETDEWEB)

    Faller, J.; Huehnerfuss, H.; Koenig, W.A.; Krebber, R.; Ludwig, P. (Univ. Hamburg (West Germany))

    1991-04-01

    The enantiomeric ratio of a chiral organic pollutant has been determined gas chromatographically for the first time at low concentrations as encountered in a North Sea water sample by using heptakis (3-O-butyryl-2,6-di-O-pentyl)-{beta}-cyclodextrin as a chiral stationary phase. As an example, the separation of the enantiomers of {alpha}-hexachlorocyclo-hexane ({alpha}-HCH) is shown herein. However, the method is expected to be generally applicable to many environmental problems that are related to chiral biogenic and anthropogenic substances and chiral degradation products. The potential of this experimental approach for a discrimination between enzymatic and nonenzymatic processes in marine and terrestric ecosystems is discussed.

  20. TCDD和B[a]P诱导大鼠肺癌变过程CYPIA1表达变化的研究%Expression of CYPIA1 in the process of rat lung carcinogenesis induced by TCDD and B[a]P

    Institute of Scientific and Technical Information of China (English)

    肖和龙; 吕嘉春; 黎银燕; 宾晓农; 谭敏; 刘小琦

    2013-01-01

    目的:利用四氧二苯二氧杂环己二烯(TCDD,二噁英)和苯并(a)芘(B[a]P)致大鼠肺癌的动物模型,研究肺癌变过程中CYPIA1基因mRNA和蛋白水平的表达.方法:应用RT-PCR方法及荧光免疫法检测大鼠正常肺组织、癌前病变组织和肺癌组织中CYPIA1基因mRNA的表达及CYPIA1基因在肺组织蛋白水平的表达,评价CYPIA1基因在肺癌变过程的作用.结果:CYPIA1 mRNA/β-actin比值在TCDD、TCDD+ B[a]P、B[a]P致癌组及对照组分别为0.956 4±0.328 2、1.153 3±0.432 6、0.252 4±0.103 2和0.093 6±0.032 7;在大鼠正常肺组织、正常增生、癌前病变和肺癌组织中分别为0.105±0.098、0.235±0.108、1.127±0.295和1.564±0.421.结果表明,CYPIA1 mRNA在TCDD+B[a]P、TCDD致癌组有较强表达,在肺癌前病变和肺癌组织中有较强表达;CYP1A1蛋白表达灰度值在TCDD、TCDD+ B[a]P、B[a]P致癌组及对照组分别为41.76±4.82、46.28±4.32、31.02±3.16和18.75±2.27,在大鼠肺正常组织、正常增生、癌前病变和肺癌组织中分别为19.77±2.74、26.71±3.32、43.95±3.98和47.38±4.96.结果表明,CYP1A1蛋白在TCDD+ B[a]P和TCDD致癌组有较强表达,在肺癌前病变和肺癌组织中有较强表达.结论:TCDD和B[a]P对CYPIA1有较好的诱导作用,CYPIA1高表达与肺癌的发生有着密切的关系,其在肺癌前病变和肺癌组织中的高表达,可能是肺癌前病变、肺癌发生的一个标志.%OBJECTIVE:To investigate the role of gene CYPIA1 in the process of lung carcinogenesis. METHODS: In the animal model of rats lung cancer induced by dioxin and B[a]P,the level of CYPIA1 mRNA and CYPIA1 protein expression in groups of TCDD, TCDD + B[a]P, B[a]P and control group were tested. RESULTS: The ratio of CYPIAlmRNA/p-actin in cancerogen groups of TCDD,TCDD+B[a]P, B[a]P and control group were 0. 956 4±0. 328 2, 1. 153 3 + 0. 432 6,0. 252 4 + 0. 103 2,0. 093 6 + 0. 032 7;in normal epithelium,epithelial hyperplasia,atypical hyperplasia

  1. 2,3,7,8-四氯二苯并二恶英哺乳期暴露对仔鼠牙齿的显微硬度分析%Effects of lactational exposure to 2,3 ,7,8-TCDD on tooth microhardness in SD rat offsprings

    Institute of Scientific and Technical Information of China (English)

    耿华欧; 章锦才; 屈菊兰; 王京滨

    2011-01-01

    Objective To investigate the effects of lactational exposure to 2,3,7,8- TCDD on changes of microhardness of enamel and dentine of rats. Methods The tooth model was obtained from rats exposed to TCDD in lactational phase through giving low dose of 2,3,7,8-TCDD. PD60 teeth were obtained and prepared. The upper incisors from 2,3,7,8-TCDD group and control group were cut longitudinally and polished for Vicker's microhardness measurement in the regions of the enamel and dentin. Results The depth of the formed moulage was deeper in 2,3,7,8-TCDD group. Compared with control group, the average hardness for TCDD enamel was lower, and the difference was highly significant ( 134. 9 ± 14.3 vs178.2 ± 19.6, P < 0.01 ). The same result happened to dentin area(64.9 ± 11.5vs79.6 ± 10.7 ,P <0.01 ). Conclusions 2,3,7,8-TCDD exposure may decrease microhardness of enamel and dentine and therefore it is suggested that TCDD exposure affects the quality of tooth hard tissue and the mineralization process.%目的 探讨哺乳期二恶英类物质2,3,7,8-四氯二苯并二恶英(2,3,7,8-tetrachlorodibenzo-p-dioxin,2,3,7,8-TCDD)暴露对大鼠釉质和牙本质显微硬度的影响.方法 应用给予低浓度2,3,7,8-TCDD染毒方法,建立哺乳期2,3,7,8-TCDD暴露模型,收集日龄60 d大鼠牙齿作为实验样品.2,3,7,8-TCDD暴露组和对照组大鼠下颌切牙沿牙长轴切割,抛光后在不同选择区域行维氏显微硬度的测定.结果 同对照组相比,2,3,7,8-TCDD暴露组压痕较深.釉质平均显微硬度比较,2,3,7,8-TCDD暴露组明显降低,两组差异有显著性(P<0.01).牙本质平均显微硬度比较,2,3,7,8-TCDD组较低,两组有统计学意义(P<0.01).结论 2,3,7,8-TCDD暴露对牙齿硬组织质量有影响,牙齿的机械抗力降低.

  2. Three decades (1983-2010) of contaminant trends in East Greenland polar bears (Ursus maritimus). Part 2

    DEFF Research Database (Denmark)

    Dietz, Rune; Rigét, Frank F; Sonne, Christian

    2013-01-01

    and p,p'-DDT, α- and β-hexachlorocyclohexane (HCH), HCB, octachlorostyrene, dieldrin, oxychlordane, cis- and trans-chlordane, cis- and trans-nonachlor, heptachlor epoxide and BB-153), 18 showed statistically significant average yearly declines of -4.4% (range: -2.0 to -10.8%/year) among subadult polar...

  3. 二噁英对子宫内膜异位症患者子宫内膜细胞TNF-α表达的影响%Expression of TNF-α in Endometrial Cells Exposed to 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD) in Patients with Endometriosis

    Institute of Scientific and Technical Information of China (English)

    方庆仙; 张信美; 林俊

    2011-01-01

    探讨二噁英(TCDD)在子宫内膜异位症(EMs)发病中的作用.方法:通过预实验,加入一定浓度的TCDD分别作用于11例EMs患者离体在位子宫内膜细胞和12例离体对照组子宫内膜细胞24h,应用Real-timeRT-PCR和ELISA法检测TCDD处理前后子宫内膜细胞肿瘤坏死因子-α(TNF-α)mRNA和蛋白的表达.结果:TCDD未处理前,EMs组子宫内膜细胞分泌TNF-α蛋白和mRNA水平均显著高于对照组(P<0.05).TCDD呈剂量依赖方式促进子宫内膜细胞TNF-α蛋白的分泌,以10nmol/L TCDD作用最明显(P<0.01),但TCDD对子宫内膜细胞TNF-α mRNA表达均无明显影响(P>0.05).结论:二噁英可能通过影响子宫内膜细胞TNF-α蛋白水平的表达而参与EMs的发病过程,其主要机制可能不是通过调节其转录途径.%Objective: To investigate the possible role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the pathogenesis of endometriosis(Ems). Methods: Through pre-experiment to choose a certain TCDD concentration, the entopic endometrial cells from 11 patients with endometriosis and 12 controls were treated by TCDD at a certain concentration for 24 h, the expression of messenger RNA and protein of levels of tumor necrosis factor-a(TNF-a) were measured by real-time RT-PCR and ELISA Results: The expression of messenger RNA and protein of TNF-a were significantly higher in endometrial cells from Ems group compared with the controK^O.05), ELISA showed that TCDD stimulated the expression of TNF-a protein in endometrial cells in a dose-dependant manner, and the effect was maximal at 10 nmol/L TCDD(P0.05). Conclusion: The results suggested that TCDD may be involved in the pathogenesis of endometriosis at least partly by inducing the levels of TNF-a protein expression in endometrial cells. The main mechanism that TCDD regulates the expression of TNF-a in endometrial cells may not act on the transcription level.

  4. 孕期四氯二苯对二噁英处理对子鼠颌下腺表皮生长因子和表皮生长因子受体的影响%EFFECTS OF IN UTERO EXPOSURE OF TCDD ON SYNTHESIS OF EPIDERMAL GROWTH FACTOR AND EPIDERMAL GROWTH FACTOR RECEPTOR IN SUBMANDIBULAR GLAND OF RAT OFFSPRINGS

    Institute of Scientific and Technical Information of China (English)

    韩笑宁; 王笑海; 何威

    2003-01-01

    目的研究孕期四氯二苯对二噁英(TCDD)处理对子鼠颌下腺表皮生长因子(EGF)和表皮生长因子受体(EGFR)的影响.方法孕15d大鼠给予TCDD(5 μg/kg)灌胃1次,采用免疫组织化学方法,对不同发育阶段的子鼠颌下腺进行了观察.结果在PND32,PND49d,TCDD组颌下腺EGF和EGFR的免疫反应阳性产物比对照组丰富,有显著性差异.结论孕期TCDD暴露促进了青春期和青春前期子鼠颌下腺EGF的生成和EGFR的表达.

  5. 2,3,7,8-TCDD的短期暴露对HepG2肝癌细胞内小分子代谢产物的影响%Effects of Short-Term Exposure to 2,3,7, 8-TCDD on Low-Molecular Metabolites in HepG2 Cells

    Institute of Scientific and Technical Information of China (English)

    张保琴; 张海军; 杨常青; 陈吉平

    2012-01-01

    To investigate the mechanisms underlying metabolic toxicity and hepatotoxicity of dioxins,HepG2 cells were selected to be exposed to the most toxic dioxin,23,7,8-tetrachlorodibenz0-p-dioxin (TCDD) for 24 h,and the proliferative activity of HepG2 cells was determined by MTT assay,while low-molecular metabolites (amino acids,glucose,itrea and glycerol) were qualitatively and quantitatively analyzed by HPLC-MS/MS.Results showed that short-term TCDD exposure had little effect on the proliferative activity of HepG2 cells.Glucose consumption did not change significantly after 24 h-exposure to TCDD,but only when the concentration of TCDD increased to 1 nmol·L-1,glucose consumption showed a slight decrease.0.01 nmol·L-1 TCDD inhibited the synthesis of praline and glutamate in HepG2 cells,and the synthesis of glutamate decreased in an obvious dose-response manner.The absorbability of several amino acids (valine,tryptophan,tyrosine,methi-onine,leucine and isoleucine) was stimulated by TCDD in a dose-response manner.The productions of urea and glycerol tended to decrease with increasing TCDD concentration.After 24 h-exposure to 1 nmol·L-1TCDD,the productions of urea and glycerol decreased to 1% and 18% of that of the control group.These results demonstrated that short-term exposure to TCDD could affect low-molecular metabolites in HepG2 cells to different degrees.TCDD exerted toxicity to HepG2 cells by disturbing its metabolism.%为了研究二恶英对细胞的代谢毒性,探究其肝毒性的作用机制,以二恶英中毒性最强的2,3,7,8-四氯代二苯并-对-二恶英(TCDD)为代表污染物,以HepG2肝癌细胞为受试对象,采用四甲基偶氮唑蓝(MTT)法和高技液相色谱/串联质谱法考察了TCDD的24 h暴露对HepG2细胞的增殖活性以及细胞的葡萄糖、氨基酸、尿素和甘油等小分子代谢物的影响.结果显示,短暂的TCDD暴露对HepG2细胞的增殖活性无显著影响.24 h的TCDD暴露对细胞的葡萄糖消耗量无

  6. Effects of Lactational 2,3,7,8-TCDD Exposure to Mineral Content and Cry Stallo-graphic Properties in Tooth Enamel of SD Rat Offspring Rats%哺乳期2,3,7,8-TCDD暴露仔鼠牙齿釉质的矿物质含量和晶体特性分析

    Institute of Scientific and Technical Information of China (English)

    耿华欧; 章锦才; 东野广智; 王京滨

    2012-01-01

    Objectives To explore the relationship between lactational TCDD-exposure and the changes of dental enamel mineral content and crystallographic properties in rats. Methods: Enamel samples were obtained from TCDD - exposure group and control group. The incinerated tissue method was used to measure mineral content. The Fourier Transform Infrared spectroscopy was used to assess the crystallographic properties. Results; The mineral content in TCDD - exposed group shows a downwards trend compared to control group. Differences between two groups reach significance (secrectory-early mature enamel:57. 8 ± 8, 9 vs 42. 2 ± 10. 8,P<0. 01;mature enamel: 90. 3±15. 2 vs 75. 4±18. 5,P<0. 05). There were characteristic absorbency peak of CO32- and PO43- in all enamel samples, and the peak of CO32- in 2,3,7,8 -TCDD group was higher than the control. The display of peak and quantitative assay, the absorbency of CO32 -/PO43 - in control group decreased compared to the 2,3,7,8 -TCDD group(secrectory-early mature enamel: 0. 4170±0. 0324 vs 0.4726 ±0.0533,P<0. 0lsmature enamel:0. 3356± 0. 0427 vs 0. 3944+0. 0538,P<0. 01). The ratio of structural carbonate to phosphate in dental enamel of control group is significantly higher than 2,3,7,8 -TCDD group. Conclusion: These results indicate that in TCDD-exposed group mineral content decreased and crystallographic properties of enamel changed.%目的:探讨哺乳期内2,3,7,8-TCDD暴露对牙齿釉质的矿物质含量和晶体特性的影响.方法:分别从2,3,7,8-TCDD暴露组和对照组PD60仔鼠的牙齿釉质提取样品.应用组织灰化法测定矿物质含量.应用红外光谱技术评价晶体性质.结果:2,3,7,8-TCDD暴露组牙齿釉质矿物质含量同对照组相比出现降低情况,2组间比较,差异明显(分泌-早期成熟期釉质:57.8±8.9 Vs 42.2±10.8,P<0.01;成熟期釉质:90.3±15.2 Vs 75.4±18.5,P<0.05).所有釉质样品中均出现CO32-和PO43-特征性吸收峰,2,3,7,8-TCDD暴露组CO32-吸收

  7. CASE STUDY: DIELDRIN ATTACK IN DALYAN LAGOON

    Science.gov (United States)

    During the first two weeks of December 2005, NATO sponsored an Advanced Study Institute (ASI) in Istanbul, Turkey. Part of this ASI involved a case study of a terrorist attack, where a chemical was assumed to be dumped into Sulunger Lake in Turkey. This chapter documents the re...

  8. 维生素E对二(口恶)英染毒小鼠肝脏细胞色素P450酶基因转录的影响%Effect of Vitamin E on Transcription Activity of Liver CYP450 Gene in Mice Treated with TCDD

    Institute of Scientific and Technical Information of China (English)

    尹海萍; 徐建平; 周显青; 王迎

    2007-01-01

    目的 研究维生素E对2,3,7,8-四氯代二苯并二(口恶)英 (TCDD) 染毒小鼠肝脏细胞色素P4 50酶1A1、1A2、1B1基因转录的影响.方法 设计了5个实验组,将45只小鼠随机分为5组,5组动物给予TCDD和维生素E的水平依次为:TCDD 0 ng/kg和VE 0 mg/kg 、TCDD 100 ng/kg和VE 0 mg/kg、TCDD 100 ng/kg和VE 20 mg/kg、TCDD 100 ng/kg和VE 100 mg/kg、TCDD 100 ng/kg和VE 500 mg/kg.喂食4周后取其肝脏,用real-time PCR 法测小鼠细胞色素P450酶1A1、1A2、1B1基因mRNA水平.结果 TCDD染毒小鼠肝脏细胞色素P450酶1A1、1A2 mRNA水平与对照组相比有升高的趋势,而细胞色素P450酶1B1 mRNA水平明显降低.染毒并给予维生素E 20 mg/kg组,其肝脏CYP4501A1的mRNA水平有降低趋势,随着维生素E剂量的增加,YP450 1A1的mRNA水平反而有升高的趋势,当维生素E剂量为500 mg/kg时,其肝脏CYP450 1A1的mRNA 明显高于TCDD染毒组.CYP450 1A2的mRNA 水平随着维生素E剂量的增加有降低的趋势,在TCDD染毒并给予维生素E 500 mg/kg组,其肝脏CYP450 1A2的mRNA水平明显低于TCDD染毒组.而肝脏CYP450 1B1 的mRNA水平在染毒并给与维生素E 500 mg/kg组,与染毒组相比有上调趋势.结论 TCDD能影响或部分影响小鼠细胞色素P450酶1A1、1A2、1B1的基因转录,而维生素E能在一定程度上缓解TCDD的作用.

  9. Toxic Responses of Zebrafish Embryos to Sub-lethal Concentrations of TCDD Exposure%亚致死性浓度的二噁英在斑马鱼胚胎中所致的毒性反应

    Institute of Scientific and Technical Information of China (English)

    陈静; 理查德·彼德森; 沃沦·海德曼

    2009-01-01

    [目的]观察亚致死性浓度的二噁英(TCDD)对斑马鱼胚胎发育的毒性作用.[方法]将72 hpf(受精后小时)斑马鱼胚胎暴露于渐升的TCDD亚致死性浓度下,观察累积死亡率、心功能及颌软骨发育的变化,与对照组比较.[结果]10 pg/ml及25 pg/ml的TCDD浓度所导致的两周内的累积死亡率与对照组类似.然而在胚胎内这两种浓度的TCDD均能导致急性及亚急性心脏毒性.暴露在这两种浓度TCDD下与对照组相比,在毒物处理后的12 h、1d、2d及1周后胚胎均表现出心每搏输出量及心输出量的显著降低.最显著的发现是72 hpf胚胎在10 pg/ml的TCDD处理后1周表现出显著的每搏输出量及心输出量降低,伴轻微的心包积液.[结果]该研究表明较低浓度的二噁英污染对野生鱼类能造成威胁,而亚致死性浓度的TCDD对胚胎的颌骨发育无影响.

  10. Inhibition effects of TCDD on IgM secretion of LPS activated B lymphoma cell line CH12.LX and its mechanism study%2,3,7,8-TCDD对B淋巴瘤细胞株CH12.LX抗体分泌功能的毒性效应及机制研究

    Institute of Scientific and Technical Information of China (English)

    王颖莹; 裴莉萍; 陈纯海; 张伟; Norbert E. Kaminski

    2007-01-01

    目的 探讨2,3,7,8-四氯二苯-对-二噁英(TCDD)对B淋巴细胞株CH12.LX的抗体分泌功能的毒性效应,及其可能的受体机制.方法 以B淋巴细胞株CH12.LX为细胞模型,以ELISA法检测系列浓度TCDD处理对LPS活化CH12.LX的IgM分泌功能的影响,以RT-PCR和Western blot 法检测CH12.LX细胞内芳香烃受体(AhR)的表达水平,以及TCDD对细胞色素P450Cyp1a1的诱导效应.结果 较低浓度的TCDD(0.03 nmol/L)即对CH12.LX的IgM分泌能力产生了显著的抑制效应(P<0.05),同时TCDD(10 nmol/L)可显著诱导CH12.LX细胞内Cyp1a1 mRNA的表达(P<0.05),并于CH12.LX细胞内发现AhR有一定水平的表达.结论 TCDD对B淋巴细胞株CH12.LX存在显著的抗体分泌抑制效应;同时,推测TCDD的这一免疫毒性效应主要可能由AhR介导.

  11. Chemical contaminants, health indicators, and reproductive biomarker responses in fish from rivers in the Southeastern United States

    Science.gov (United States)

    Hinck, J.E.; Blazer, V.S.; Denslow, N.D.; Echols, K.R.; Gale, R.W.; Wieser, C.; May, T.W.; Ellersieck, M.; Coyle, J.J.; Tillitt, D.E.

    2008-01-01

    Largemouth bass (Micropterus salmoides) and common carp (Cyprinus carpio) were collected from 13 sites located in the Mobile (MRB), Apalachicola-Flint-Chattahoochee (ARB), Savannah (SRB), and Pee Dee (PRB) River Basins to document spatial trends in accumulative chemical contaminants, health indicators, and reproductive biomarkers. Organochlorine residues, 2,3,7,8-tetrachlorodibenzo-p-dioxin-like activity (TCDD-EQ), and elemental contaminants were measured in composite samples of whole fish, grouped by species and gender, from each site. Mercury (Hg) and polychlorinated biphenyls (PCBs) were the primary contaminants of concern. Concentrations of Hg in bass samples from all basins exceeded toxicity thresholds for piscivorous mammals (> 0.1????g/g ww), juvenile and adult fish (> 0.2????g/g ww), and piscivorous birds (> 0.3????g/g ww). Total PCB concentrations in samples from the MRB, ARB, and PRB were > 480??ng/g ww and may be a risk to piscivorous wildlife. Selenium concentrations also exceeded toxicity thresholds (> 0.75????g/g ww) in MRB and ARB fish. Concentrations of other formerly used (total chlordanes, dieldrin, endrin, aldrin, mirex, and hexachlorobenzene) and currently used (pentachlorobenzene, pentachloroanisole, dacthal, endosulfan, ??-hexachlorocyclohexane, and methoxychlor) organochlorine residues were generally low or did not exceed toxicity thresholds for fish and piscivorous wildlife. TCDD-EQs exceeded wildlife dietary guidelines (> 5??pg/g ww) in MRB and PRB fish. Hepatic ethoxyresorufin O-deethylase (EROD) activity was generally greatest in MRB bass and carp. Altered fish health indicators and reproductive biomarker were noted in individual fish, but mean responses were similar among basins. The field necropsy and histopathological examination determined that MRB fish were generally in poorer health than those from the other basins, primarily due to parasitic infestations. Tumors were found in few fish (n = 5; 0.01%); ovarian tumors of smooth muscle

  12. Effect of intrauterine exposure to TCDD on key steroidogenesis genes in placenta of male fetal rat%宫内TCDD暴露对雄性胎鼠胎盘类固醇生成关键基因的影响

    Institute of Scientific and Technical Information of China (English)

    韩伟; 马静; 陈曦; 刘亚男; 张爱莲; 陈京山; 冷玲; 闫欢

    2014-01-01

    目的 探讨关键生长期宫内2,3,7,8-四氯二苯并二(噁)英(TCDD)暴露对子代生长发育和胎盘类固醇合成关键基因的影响.方法 孕SD大鼠随机分为TCDD染毒组(100,500 ng/kg)和对照组(纯玉米油),记录GD 19 d妊娠结局并测定胎鼠生长发育指标,实时荧光定量PCR法测定雄胎鼠胎盘类固醇生成关键基因(P450scc、P450c17、3β-HSD)的表达水平.结果 (1)孕鼠剖宫日当天各组的肝脏重量和脏器系数差别有统计学意义(P<0.05),500ng/kg组孕鼠肝脏质量小于对照组;(2)对照组与染毒组不良妊娠率差别有统计学意义(P<0.05);(3)染毒组的雄胎鼠体重均低于对照组,胎盘重量均高于对照组;(4)染毒组雄胎鼠的一般生长发育指标均低于对照组,但仅100ng/kg组雄性胎鼠尾长与对照组比较差别有统计学意义(P<0.05);(5)染毒组雄鼠胎盘P450scc、P450c17、3β-HSD mRNA表达均低于对照组.对照组胎盘P450scc、P450c17、3β-HSDmRNA表达水平分别为100 ng/kg组和500ng/kg组的1.63、1.42、1.49倍和1.63、1.14、1.41倍.结论 性别性腺决定期宫内TCDD暴露可对雄胎鼠一般生长指标产生影响,并可影响其胎盘类固醇生成关键基因的表达.

  13. Toxicology and carcinogenesis studies of a mixture of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Cas No. 1746-01-6), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (Cas No. 57117-31-4), and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (Cas No. 57465-28-8) in female Harlan Sprague-Dawley rats (gavage studies).

    Science.gov (United States)

    2006-09-01

    DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized, they accumulate in body tissues, mainly adipose, resulting in chronic lifetime human exposure. Since human exposure to DLCs always involves a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) are not manufactured commercially other than for scientific research purposes. The main

  14. Detection of persistent organic pollutants in the Mississippi Delta using semipermeable membrane devices

    Science.gov (United States)

    Zimmerman, L.R.; Thurman, E.M.; Bastian, K.C.

    2000-01-01

    From semipermeable membrane devices (SPMDs) placed in five Mississippi Delta streams in 1996 and 1997, the persistent organic pollutants (POPs) aldrin, chlordane, DCPA, DDT, dieldrin, endrin, heptachlor, mirex, nonachlor, and toxaphene were detected. In addition, the insecticides chlorpyriphos, endosulfan, and hexachlorocyclohexanes were detected. Two low-solubility herbicides not detected commonly in surface water, pendimethalin and trifluralin, were also detected. Copyright (C) 2000 Elsevier Science B.V.

  15. Concentrations of Polychlorinated Biphenyls (PCB’s), Chlorinated Pesticides, and Heavy Metals and Other Elements in Tissues of Belugas, Delphinapterus leucas, from Cook Inlet

    OpenAIRE

    Becker, Paul R.; Krahn, Margaret M.; Mackey, Elizabeth A.; Demiralp, Rabia; Schantz, Michele M.; Epstein, Michael S.; Donais, Mary Kate; Porter, Barbara J.; Derek C G Muir; Wise, Stephen A.

    2000-01-01

    Tissues from Cook Inlet beluga whales, Delphinapterus leucas, that were collected as part of the Alaska Marine Mammal Tissue Archival Project were analyzed for polychlorinated biphenyls (PCB’s), chlorinated pesticides, and heavy metals and other elements. Concentrations of total PCB’s (ΣPCB’s), total DDT (ΣDDT), chlordane compounds, hexachlorobenzene (HCB), dieldrin, mirex, toxaphene, and hexachlorocyclohexane (HCH) measured in Cook Inlet beluga blubber were compared with those reported for b...

  16. 2,3,7,8-四氯苯并二噁英(TCDD)短期染毒可造成着床前胚胎丢失并伴随雌性生殖器官中毒物相关蛋白的诱导表达%Short Time Exposure of TCDD Causing Loss of Implantation Failure of Embryos and Its Associated with Induced Expression of Relevant Proteins

    Institute of Scientific and Technical Information of China (English)

    黄莉; 黄韧; 冯媛瑜; 刘寒英; 丘剑峰; 李冰

    2010-01-01

    为探明妊娠早期胚胎的丢失是否与卵巢、输卵管、子宫组织受到2,3,7,8-四氯苯并二噁英(TCDD)直接毒害有关,检测了NIH小鼠胚胎着床前期和后期TCDD暴露对胚胎毒性影响的敏感性,并利用免疫组化方法分析了模型动物肝脏、子宫、输卵管和卵巢组织中TCDD所引起的AhR、ARNT以及Cyp1a2分子标记物的变化.检测发现:妊娠第9d,100ng·kg-1·d-1剂量TCDD经口染毒,造成胚胎着床数量减少,且着床前期暴露的影响大于着床后期;子宫蜕膜反应受到明显抑制;胚胎迁移率没有明显变化,但胚胎数量减少.免疫组织化学分析发现正常组小鼠的肝脏、子宫、输卵管和卵巢组织中有AhR和Cypla2弱阳性信号表达,ARNT有细胞核的强阳性信号表达;妊娠第1~8d、第1~3d和第4~8d处理组小鼠肝脏、子宫、输卵管和卵巢组织中的AhR、Cypla2的阳性面积和光密度值均高于正常组;随处理时间和组织蓄积量的增加,ARNT在组织中的变化由胞核(妊娠第1~3d组)表达到胞浆(妊娠第4~8d组)表达,然后完全无表达(妊娠第1~8d组).以上研究结果表明:TCDD对早期妊娠小鼠子宫、输卵管和卵巢组织中的AhR、ARNT和Cypla2的激活和代谢方式与肝脏相同,说明雌性生殖系统中的组织有TCDD蓄积和代谢活性,这可能是导致早期胚胎迁移、着床等过程改变,造成胚胎丢失的重要原因.

  17. Increasing transformation efficiency by topoisomerase Ⅱ and its application for cloning of a γ-hexachlorocyclohexane dehydrochlorinase gene linA-like from a bacterial community%利用拓扑异构酶Ⅱ提高转化效率及其在从细菌群落中克隆六六六γ异构体脱氯化氢酶基因中的应用

    Institute of Scientific and Technical Information of China (English)

    李丽观; 杜宏伟; 王晓琳; 蒋丽娟; 杨柳燕; 武俊

    2011-01-01

    A simple modification was developed for construction of genomic/metagenomic libraries by T-vectors.Topoisomerase Ⅱ was employed to introduce superhelical turns into relaxed circular T-A recombinant molecules,which greatly increased the transformation efficiency.By using this technique,a metagenomic library was constructed and a γ-hexachlorocyclohexane dehydrochlorinase gene linA-like was screened from it.%一个简单的技术上的调整被应用于利用T载体构建的基因组或宏基因组文库策