• 제목/요약/키워드: TCDD

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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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    • 제29권7호
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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.

Similarity of Gene Expression Profiles in Primary Brain Tumors with the Toxic Mechanism by Environmental Contaminants

  • Kim, Yu-Ri;Kim, Ki-Nam;Park, Yoon-Hee;Ryu, Yeon-Mi;Sohn, Sung-Hwa;Seo, Sang-Hui;Lee, Seung-Ho;Kim, Hye-Won;Lee, Kweon-Haeng;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • 제1권3호
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    • pp.209-215
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    • 2005
  • Recently, a large number of clinical experiments have shown that exposure of organic pollutants lead to various cancers through the abnormal cell growth. Environmental pollutants, such as 2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs), are carcinogen and are known to cause the cognitive disability and motor dysfunction in the developing of brain. The effects of these pollutants on neurodevelopmental disorder is well established, but the underlying mechanism(s) and similarity of gene expression profiles in human brain tumors with organic pollutants still remain unclear. In this study, we first examined the gene expression profiles in glioblastomas compared with meningioma that are kinds of primary human brain tumor by using human cDNA microarray. The results of cDNA microarray analysis revealed that 26 genes were upregulated (Z-ratio>2.0) and 14 genes were downregulated (Z-ratio<-2.0) in glioblastoma compared with meningioma. From the altered gene patterns, mitogen-activated protein kinase (MAPK) signaling related genes, such as MAP2K3, MAP3K11 and jun activated domain binding protein, and transcription factors, such as UTF2 and TF12, were upregulated in glioblastoma. Also, we tried to investigate the relation between important genes up- and down-regulated in giloblastoma and various organic pollutants. Therefore, the identification of changes in the patterns of gene expression may provide a better understanding of the molecular mechanisms involved in human primary brain tumors and of the relation between gene expression profiles and organic pollutants in brain tissue.

Daisdzein이 Benzo(k)fluoranthene에 의한 CYP1B1 유전자조절 작용에 미치는 영향 (Effect of Daisdzein on the Benzo(k)fluoranthene Regulated CYP1B1 Gene Expression)

  • 서미정;김여운;신윤용
    • 한국환경성돌연변이발암원학회지
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    • 제24권4호
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    • pp.198-205
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    • 2004
  • Cytochrome P4501B1(CYP1B1) is known to be inducible by xenobiotic compounds such as policyclic aromatic hydrocarbon(PAH) and dioxins such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). And these induction of CYP1B1 is also regulated by many categories of chemicals. In order to investigate the effects of several chemicals on CYP1B1 gene expression in Hepa-I and MCF-7 cells, 5' flanking DNA of human CYP1B1 was cloned into pGL3 basic vector containing luciferase gene, and then transfected into these cells. After treatment of chemicals, the luciferase activity was measured. CYP1B1 enzyme metabolize PAHs and estradiol. CYP1B1 metabolize estradiol to 4-hydrozyestradiol that is considered as carcinogenic metabolite. Recent industrialized industrialized society, human has been widely been exposed to widespread environmental contaminants such as PAHs(polycyclic aromatic hydrocarbon) that are originated from the imcomplete combustion of hydrocarbons. PAHs are known to be ligands of the AhR(aryl hydrocarbon receptor). Induction of cytochrome P4501B1(CYP1B1) in cell culture is widely used as a biomarker for PAHs. Therefore we have studied the effect of PAHs in the human breast cancer cells MCF-7 to evaluate bioactivity of PAHs. We have used the United State of America EPA selected 13 different PAHs, PAHs mixtures and extracts from environmental samples to evaluate the bioassay system. We examined effects of PAHs on the CYP1B1-luciferase reporter gene and CYP1B1 mRNA level. Benzo(k)fluoranthene and dibenzo(a, h)anthracene showed strong response to CYP1B1 promoter activity stimulation, and also CYP1B1 mRNAs increase in MCF-7 cells in a concentration-dependent manner. RT-PCR analysis indicated that PAHs significantly up-regulate the level of CYP1B1 mRNA. Some flavonoids such as genistein, daidzein, chrysin, naringenin and morin were also investigeted. These flavonoids decreased B(k)F infuced luciferase activity at low concentration. But, these flavonoids exhibited stimulatory effect at high concentration.

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파월국군장병의 고엽제 위해에 관한 예비적 역학조사 (A Preliminary Epidemiologic Study on Korean Veterans Exposed to Herbicides in Vietnam War)

  • 김정순;임현술;이홍복;이원영;박영주;김성수
    • Journal of Preventive Medicine and Public Health
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    • 제27권4호
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    • pp.711-734
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    • 1994
  • Among chemical agents in herbicides, dioxin (2, 3, 7, 8-tetrachloro dibenzo-$\rho$-dioxin : TCDD), a chemical contaminant in herbicides sprayed during the Vietnam War has been known to be the major agent causing toxic effects. Approximately 320,000 korean soldiers participated the Vietnam War from 1964 to 1974. Although the potential hazards of the herbicides among Korean veterans exposed were implicated, the problem had not been a public issue until 1991 when Korean veterans were informed U.S. companies, the herbicides manufacturer payed fund, from which a trust fund for New Zealand and Australian Class members were established in 1985. After a series of appeals and demonstration by the Korean Veterans demanding medical care and compensation for their serious health damages, a bill of medical care and compensation for herbicides victims was promulgated in March 1993 and become effective from May 1993, This study was carried out with two major objectives : the first to understand the health problems caused from the herbicides by reviewing literatures published, and the second to examine the nature and extent of health impacts among Korean veterans exposed and to develop valid study methods for the major study by interviewing and reviewing records on a part of veterans (638 persons) registered and completed medical examination in Seoul Veterans Administration Hospital from June to October 1993. The results obtained are as followings: 1. The literature review of 107 papers revealed that 1) Dioxin is teratogenic, carcinogenic and affects almost all organs including nervous, endocrine, and reproductive systems in animal experiments. 2) The diseases showing evidence of causal association were Hodgkin's disease, non-Hodgkin's disease, lung cancer, lymphoma, soft tissue sarcoma, chloroacne and polyneuropathy when judged on the basis of consistency in study results and biological plausibility. 2. Interview and medical record review study on 638 veterans, though limited validity owing to lack of control group, crude estimates of dioxin exposure levels (no biomarkers measurable), and uncertainty of diagnosis, showed that: 1) Most of the study subject's were in their 40's of age and had been dispatched to Vietnam during the period from $1965{\sim}1970$ around one year. 2) Most frequently complained symptoms in medical examination were motor weakness (32%), sensory abnormalities in extremities (23%), skin diseases (22%), and pain in extremities (20%) whereas in Interview they were more frequent in order of skin problem (44%), motor weakness (38%), sensory abnormalities and pain in extremities(17% and 19% each). Kappa indices on the same category of complaints between two sources of information were variable and relatively low. 3) On medical examination, only a part of the 638 subjects had initial impression (442 pts) and final diagnosis (218 pts) suggesting decision making on diagnosis appeared to be difficult even with all available modern medical technologies: in initial impression disorders from peripheral and central neuropathy were predominant whereas in final diagnosis various types of skin disorder were most frequent 4) When dose-response relationship between several conditions (from questionnaire) and arbitrary exposure scores were examined by CMH linear trend test, spontaneous abortion, sexual problems and health problem of offsprings showed statistically significant linear trends. However, pregnancy, accident and suicidal attempts did not show any relationship in this study capacity. 5) Among complaints, psychosis and neurosis (anxiety, phobia) in interview study, and memory disorder and psychosis in medical record study revealed linear trend. 6) Skin disorder was the only condition showing linear trend in initial impression and none in final diagnosis on medical examination. Even though objective to select out dioxin-related disease or group of diseases from this study was not achieved the research experiences provided firm basis for developing various methodological approaches. 3. From this preliminary study we concluded that a larger scale major epidemiologic study on health impacts of herbicides among Korean veterans exposed is not only Indispensible but also well designed study with more valid exposure information and diagnosis may be able to establish causal relationship between certain groups of diseases and exposure to the herbicides among Korean veterans.

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