• Title/Summary/Keyword: 2,3,7,8-TCDD

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Regulation of Cyp 1A1 Gene Expression by Retinoic Acid Receptor, Retinoid X Receptor and Constitutive Androstane Receptor in Rainbow Trout Hepatoma Cells(Rth 149)

  • Kim, Ji-Sun;Yang, So-Yeun;Seo, Mi-Jung;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.136-136
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    • 2003
  • Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CVP1A1 gene.(omitted)

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Effect of Benzo(k)fluoroanthene and Genistein on CYP1A1 Gene Expression in Human Breast Cancer MCF-7 Cells. (사람 유방암 세포 MCF-7에서 Benzo(k)fluoroanthene과 genistein이 CYP1A1 유전자 발현에 미치는 영향)

  • Yang, So-Yeon;Min, Kyung-Nan;Shin, Yhun-Yhong
    • Environmental Mutagens and Carcinogens
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    • v.24 no.3
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    • pp.128-136
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    • 2004
  • CYP1A1 is known to be inducible by xenobiotic compouds such as polyciclic aromatic hydrocarbons(PAHs) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). These chemicals have been identified worldwide and can have a significant impact on the human health and well being of human and wildlife. Given these issues, the detection and quantification of these chemicals in biological, environmental and food samples is important. First, we investigated the effect of on CYP1A1 promoter activity, 7-ethoxyresorufin-O-deethylase(EROD) activity and CYP1A1 mRNA expression induced by benzo(k)fluoranthene(B(k)F) in MCF-7 cells. We found that B(k)F significantly up-regulates the level of CYP1A1 prompter activity, EROD and CYP1A1 mRNA. When cells were treated with genistein, it was not changed that EROD and CYP1A1 mRNA, compared to that of control. However, genistein inhibited the B(k)F-induced CYP1A1 promoter activity and mRNA level at high concentration. Furthermore, in this study, effects of HDAC(histone deacetvlase) inhibitors on human prostate cancer cells proliferation were examined. HC-toxin, SAHA and TSA inhibited cell proliferation in PC3 cells. A novel HDAC inhibitor, IN2001 also suppressed the growth of PC3 cells. And IN2001 and SAHA increased S phase and G2/M phase at 12 hrs treatment but cells were arrested G0/G1 phase at 45 hrs treatment. The HC-toxin treatment for 24 hrs and 48 hrs increased G0/G1 at low concentration ($0.1\mu\textrm{m}$) but increased G2/M at more than concentration of $1\mu\textrm{m}$. TSA increased G2/M phase. These findings height the possbility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of prostate cancer.

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Comparative Risk Assessment Methodology: An Application to Air Pollution (비교 위험도 평가 방법의 대기 오염에 대한 적용 연구)

  • Lee, Jin-Hong
    • Journal of Korean Society for Atmospheric Environment
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    • v.8 no.2
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    • pp.100-104
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    • 1992
  • The research in this paper centers on a comparative risk assessment for nearby air pollution by carcinogenic metal emission from municipal solid waste incinerators. If a substance is identified as a potential human carcinogen, the carcinogenicity may be related to the chemical form of a substance and the route of exposure. This type of information with regard to carcinogenic uncertainty is incorporated into hazard quantification. In addition to the dioxin emission, the metal emission from municipal solid waste incineration is found to be a major contributor to human cancer risk via the inhalation route. The magnitude of risk by metals is about 5 times greater than that of risk by dioxins. Hexavalent form of chromium and cadmium compounds are major contributors to cancer risk from metal emission. In addition, hexavalent chromium is known to be human carcinogen while 2,3,7,8-TCDD is known to be only probable human carcinogen.

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Endocrine Disruptive Potentials in Surface Water Samples from Taihu Lake, Yangtze Delta

  • Shen, L.;Lin, G.F.;Shen, J.H.
    • Toxicological Research
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    • v.17
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    • pp.319-321
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    • 2001
  • Taihu Lake is a major water source for part of Yangtze Delta, which is one of the most urbanized and economically prosperous areas in China. In last couple of decades, some parts of the lake were highly polluted due to eutrophication. This study analyzed dioxin-like potential and mutagenic potential in surface water samples from Taihu Lake. The samples were prepared by XAD-2 resin procedure. A batch of biological assays, including dioxin-like potential microassay with the rat hepatocyte cell line H411E, and Ames test was employed in the research. Results showed that jour water samples have high content of dioxin-like biological potential, the highest activity TEQ to 2,3,7,8-TCDD was 48 pg/ι in sample 1. The mutagenic effect with reading-frame shifting mechanism was confirmed in 3 of 4 samples. The effective sewage treatment facilities and reliable monitoring surveillance system are urgently needed for this area.

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Evaluation for Concentration of Residual PCDD/Fs in Pig Feed (돼지사료 중의 다이옥신 잔류 평가)

  • Ahn, Yun-Gyong;Shin, Jeoung-Hwa
    • The Korean Journal of Community Living Science
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    • v.23 no.2
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    • pp.129-136
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    • 2012
  • Dioxins are chemical substances that are not properly decomposed degradation under natural photochemical, biological and chemical conditions in the environment, and bio-accumulate through the food chain, so pose a risk of causing adverse effects to human health and the environment. Ninety seven percent of human exposure to dioxins comes through meat, fish, dairy consumption and so on. Pork is the largest proportion meat aspect of daily intake in the Korean food. Pigs are three times more than Cattle in terms of breeding population and production amount in the world, and the amount is increasing every year. Therefore, it is necessary to monitor the exposure level of dioxins in pig's body. Also, it is required to evaluate the presence of these chemical substances in the pig's feed grain such as corn, soybeans, and tallow. The purpose of this study was to evaluate PCDD/Fs in pig's feed to search the origin of PCDD/Fs. Feed samples obtained were wheat from East Europe, corn from South America and America, soybean meal from Korea, America, South America and India and tallow from Korea. The preparation of samples was based on the EPA method 1613. Instrumental analysis was based on the use of high resolution gas chromatography coupled to high resolution mass spectrometry (HRGC/HRMS). The concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD), which are the most toxic potent dioxins, were not observed in any of the samples. However OCDD was detected in most of the samples. The TEQs in the feed samples were ranged from 0 pg TEQ/g to 0.09841 pg TEQ/g. Especially, the high level of TEQs was observed in the samples of wheat from East Europe and soybean meal from Korea.

Effects of Formononetin on the Aryl Hydrocarbon Receptor and 7,12-Dimethylbenz[a]anthracene-induced Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells

  • Han, Eun-Hee;Jeong, Tae-Cheon;Jeong, Hye-Gwang
    • Toxicological Research
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    • v.23 no.2
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    • pp.135-142
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    • 2007
  • Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

Effect of Biochanin A on the Aryl Hydrocarbon Receptor and Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells

  • Han, Eun-Hee;Kim, Ji-Young;Jeong, Hye-Gwang
    • Archives of Pharmacal Research
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    • v.29 no.7
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    • pp.570-576
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    • 2006
  • Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

Effects of Dioxin Exposed in Human by Using Radioactive cDNA Microarray

  • Ryu, Yeon-Mi;Kim, Ki-Nam;Kim, Hye-Won;Sohn, Sung-Hwa;Lee, Seung-Ho;Kim, Yu-Ri;Seo, Sang-Hui;Lee, Seung-Min;Lee, Eun-Il;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.2 no.1
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    • pp.35-47
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    • 2006
  • 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) are well known as the most toxic environmental compound in these days. Many researches are reported that dioxin produces multiple toxic effects, such as endocrine toxicity, reproductive toxicity, immunotoxicity and cancer. In this study, we carried to discover novel evidence for previously unknown gene expression patterns in human exposed to dioxin by using radioactive cDNA microarray. 548 workers who were divided into experimental and control groups according to their urinary Naphthol levels were enrolled in our study. Blood mRNA in human was isolated, and the gene expression profiles were analyzed by cDNA microarray. Gene expression analysis identified 52 genes which exhibited a significant change. In our study, most notably, genes involved in cell cycle, cell proliferation, signal transduction and apoptosis in human exposed to dioxin, such as CCND3, TSHR, and EFRN5, were up-regulated. In the current study, we observed gene expression of people that are exposed to dioxin using radioactive cDNA microarray. Through these results, we suggest when objects are exposed to toxic compounds, such as dioxin, the radioactive cDNA microarray may be using in sensitively detecting of cancerous change.

Fast Analytical Method of PCDD/Fs in Water by Combination of Disk Type Solid Phase Extraction and Column Coupling Chromatography (디스크타입 고상추출장치 및 컬럼커플링을 이용한 물시료의 PCDD/Fs 간이분석법)

  • Choi, Jae-won;Moon, Bu-shik;Kim, Kyoung-sim;Kim, Jung-hee;Kim, Sun-heong;Baek, Kyung-hee
    • Journal of Korean Society on Water Environment
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    • v.22 no.5
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    • pp.879-886
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    • 2006
  • The analytical methods of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs) for water sample with extremely low concentration was developed to extract large volume and to improve fast chromatography for clean up. Semi-automated solid phase extraction (SPE) system and column coupling chromatography using elution pump was optimized and applied to each processes of treatment plant. Results of disk type SPE indicated that this system was applicable below 40 L of aqueous sample with a flow rate of 0.08 ~ 0.2 L/min. Average recoveries of SPE using labeled sampling spike of $^{37}Cl$-2,3,7,8-TCDD was 97%. Column coupling method resulted in reduced clean up time, solvent volume, increased average recoveries with constant elution rate. The combined methods were applied to the monitoring of drinking water treatment plant. Limits of detection (LOD) of each process were calculated. For example, LOD of raw and treated water ranged 0.094~0.968 pg/L and 0.028~0.364 pg/L, respectively. Combined methods of extraction and cleanup techniques provided fast analysis of PCDD/Fs with high accuracy and low LODs for water samples.

Chronic Exposure to Chlorophenol Related Compounds in the Pesticide Production Workplace and Lung Cancer: A Meta-Analysis

  • Zendehdel, Rezvan;Tayefeh-Rahimian, Raana;Kabir, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5149-5153
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    • 2014
  • Background: Chlorophenols (CPs) and related phenoxyacetic acids (PAs) are pesticide groups contaminated with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during production. PAs and CPs exposure is associated with risk of cancer, but the situation regarding lung cancer has not been clearly defined. We proposed a meta-analysis of published researches to evaluate relationship between chronic exposure to PAs and CPs in pesticide production workplaces and the risk of lung cancer. Materials and Methods: After searching PubMed, Scopus, Scholar Google, Web of Sciences until August 2013, the association between chronic PAs and CPs exposure in production workplace and lung cancer was studied in 15 cohort studies. The standardized mortality rate (SMR) and 95% confidence intervals (CI) were collected from the papers. We used random or fixed-effects models, Egger test, funnel plot and meta regression in our analysis. Results: Five papers with six reports were included in the final analysis. The standardized mortality rate for lung cancer from the random model was 1.18 (95% CI: 1.03-1.35, p=0.014) with moderate heterogeneity. Publication bias was not found for included studies in meta-analysis (p=0.9). Conclusions: Our findings has strengthen the evidence of lung cancer from chronic exposure to chlorophenol related compounds (PAs, CPs).