• Title/Summary/Keyword: 2,3,7,8-Tetrachlorodibenzo-${\rho}$-dioxin

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Tumorigenic Effects of 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin in Normal Human Skin and Lung Fibroblasts (사람의 정상 피부세포 및 폐세포의 발암에 미치는 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin의 영향)

  • Kang, Mi-Kyung;Ryeom, Tai-Kyung;Kim, Kang-Ryune;Kim, Ok-Hee;Kang, Ho-Il
    • Environmental Mutagens and Carcinogens
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    • v.26 no.3
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    • pp.77-85
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    • 2006
  • 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

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Chemical Transformation of Human Keratinocytes by 2,3,7,8-Tetrachlorodibenxo-$\rho$-dioxin

  • Kang, Mi-Kyung;Choi, Young-Sill;Ryeom, Tai-Kyung;Eom, Mi-Ok;Park, Mi-Sun;Jee, Seung-Won;Kim, Kang-Ryune;Kim, Ok-Hee;Kang, Ho-Il
    • Environmental Mutagens and Carcinogens
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    • v.26 no.3
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    • pp.69-76
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    • 2006
  • 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) is a ubiquitous, persistent environmental contaminant and the most powerful carcinogen categorized by IARC. Although the mechanism of carcinogenesis by TCDD is poorly understood, several studies have shown that the skin is one of target organs far TCDD. In this study, we investigated the neoplastic transformation of human keratinocyte-derived cell line, HaCaT, by chemical transformation method using N-methyl-N'-nitro-N-nitrorsoguanidine(MNNG) and TCDD. We found that subsequent exposure to TCDD for 3 weeks after initial exposure to MNNG markedly induced transformed cells. It was suggested that TCDD can act as a potent promoter in HaCaT cells. Furthermore, these transformed cells showed morphological alternations in soft agar and increased telomerase activity. Therefore, the TCDD treatment of HaCaT cells by initiated with MNNG could promote neoplastic transformation without stimulation by exogenous growth factors. As a result, TCDD had a strong potency as a promoter in nontumorigenic immortalized human epidermal keratinocytes.

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Effect of Saponin Fraction from Platycodon grandiflorum on Clinical Chemical Changes in TCDD (2,3,7,8-Tetrachlorodibenzo-ρ-dioxin)-induced Rat Toxicity

  • Kwak, Yi-Seong;Moon, You-Jin;Kyung, Jong-Soo;Kim, Tae-Hwan;Rhee, Man Hee
    • Biomedical Science Letters
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    • v.26 no.2
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    • pp.66-74
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    • 2020
  • This study was carried out to investigate the protective effect of crude saponin from Platycodon grandiflorum on Clinical chemical parameters in male rats acutely exposed to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Crude saponin was prepared from Korean Platycodon grandiflorum with Diaion HP-20 adsorption chromatography after extraction of 80% ethanol at 75℃. The crude saponin was confirmed by thin layer chrmatography. When compared with ginseng saponins, the crude saponin had both a few number of saponins and a broad distribution. Forty male rats (200±20 g) were divided into 4 groups. Normal control (NC) group received vehicle and saline; TCDD-treated (TT) group received TCDD (40 ㎍/kg, single dose) intraperitoneally; Platycodon grandiflorum saponin (PG5 and PG10) groups received crude saponin 5 mg/kg and 10 mg/kg (p.o), respectively, for 2 weeks before 1 week of TCDD-exposure. Increase of body weight was retarded greatly by TCDD-exposure. Body weight of animals in TT group was significantly decrease after 2 days of TCDD-exposure. However, body weights of animals in PG groups increased through the experimental perimental period, although the increasing rate was slower than that of NC group. Increases in contents of blood glucose, total cholesterol and triglyceride (TG) and activities of amylase, lipase, AST, ALT and LDH by toxic action of TCDD were significantly attenuated by crude saponin from Platycodon grandiflorum (P<0.05). In conclusion, these results suggest that crude saponin prepared from Korean Platycodon grandiflorum might be a member of useful protective agents against TCDD, which is one of the environmental hormones.

Effect of Crude saponin from Red-ginseng efflux on Blood biochemical parameters in Rats Acutely Exposed to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) (홍삼유출액으로부터 분리한 조사포닌이 TCDD (2,3,7,8-Tetrachlorodibenzo-ρ-dioxin)로 급성독성을 유도한 흰쥐의 혈액 생화학지수에 미치는 영향)

  • Kwak, Yi-Seong;Kyung, Jong-Soo;Song, Young-Bum;Wee, Jae-Joon;Park, Jong-Dae
    • Journal of Ginseng Research
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    • v.30 no.1
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    • pp.8-14
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    • 2006
  • This study was carried out to investigate the protective effect of crude saponin from red ginseng efflux (RGE-CS) on biochemical parameters in male rats acutely exposed to 2,3,7,8-tetrachlorodibenzo-$\rho$-dioxin (TCDD). Forty male rats ($200{\pm}20g$) were divided into 4 groups. Normal control group (NC) received vehicle and saline; only TCDD-treated group (TT) received TCDD ($5{\mu}g/kg$, single dose) intrperitoneally; RGE-CS 20 received 20 mg/kg of crude saponin i.p. for 4 weeks from 1 week before TCDD-exposure; RGE-CS 40 also received 40 mg/kg of crude saponin i.p. for 4 weeks from 1 week before TCDD-exposure. Body weight of TT group was significantly decreased after TCDD-exposure. However, body weight of crude saponin groups increased throughout the experimental period, although the increasing rate was slower than that of NC group. Decrease in body weight was not observed during the experimental period in RGE-CS 40. Increases in triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), AST, ALT and $Fe^{2+}$ levels by TCDD intoxication were significantly attenuated by the RGE-CS treatment. Decrease in glucose, amylase, lactate dehydrogenase (LDH) and creatinine kinase (CK) by TCDD also were inhibited by the RGE-CS. These results suggest that saponin from red-ginseng efflux might be a useful protective agent against TCDD, an endocrine disrupter.

Analysis of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Induced Gene Expression Profile in Hairless Mice Skin Using Pathway Specific cDNA Microarray

  • Ryeom, Tai-Kyung;Kang, Ho-Il;Kang, Mi-Kyung;Eom, Mi-Ok;Park, Mi-Sun;Jee, Seung-Wan;Kim, Ok-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.179-179
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    • 2003
  • 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanisms of TCDD-induced carcinogenesis are poorly understood, it considered to be non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1).(omitted)

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Effect of Red Ginseng Saponin Fraction on the Blood Components of Male Guinea Pigs with Acute Toxicity induced by 2,3,7,8-Tetracholorodibenzo-ρ-dioxin (TCDD) (홍삼의 사포닌이 다이옥신에 의한 급성독성 유도 웅성 기니피그의 혈액성분에 미치는 영향)

  • Kim, Byung-Weon;Lee, Yoon-Bok;Park, Jae-Seung;Park, Ji-Won;Hwang, Seock-Yeon
    • Journal of Digital Convergence
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    • v.11 no.4
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    • pp.339-350
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    • 2013
  • The decreased body, liver, kidney, spleen and testis weights of guinea pigs by TCDD (2,3,7,8-tetracholorodibenzo-${\rho}$-dioxin) treatment (TT) were statistically significantly increased after treating red ginseng saponin fraction (SF) (p>0.01). After treated with SF, the decreased hematocrits values and numbers of RBC and platelet, activity of amylase and lactate dehydrogenase, levels of uric acid, total protein and albumin by TT were increased, and the increased numbers of WBC, levels of triglyceride, total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, creatinine, blood urea nitrogen, calcium and phosphorus, activities of creatinine kinase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were decreased after treated with SF. And they all had a statistical significance (p>0.01) except for RBC, WBC, platelet, blood glucose, TC, calcium and albumin. From these results, we knew that SF mollified the acute toxicity induced by TCDD in guinea pigs.

Hormonal Effects of Several Chemicals in Recombinant Yeast, MCF-7 Cells and Uterotrophic Assays in Mice

  • Park, Jin-Sung;Lee, Beom-Jun;Kang, Kyung-Sun;Tai, Joo-Ho;Cho, Jae-Jin;Cho, Myung-Haing;Inoue, Tohru;Lee, Yong-Soon
    • Journal of Microbiology and Biotechnology
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    • v.10 no.3
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    • pp.293-299
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    • 2000
  • Many methods have been developed for screening chemicals with hormonal activity. Using recombinant yeasts expressing either human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127 (YER)] or androgen receptor [S. cerevisiae AR + 8320 (YAR)], we evaluated the hormonal activities of several chemicals by induction of ${\beta}-galactosidase$ activity. The chemicals were $17{\beta}-estradiol$ (E2), testosterone (T), ${\rho}-nonylphenol$ (NP), bisphenol A (BPA), genistein (GEN), 2-bromopropane (2-BP), dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and butylparaben (BP). To assess the estrogenicity of NP, the result of the in vitro recombinant yeast assay was compared with an E-screen assay using MCF-7 human breast cancer cells and an uterotrophid assay using ovariectomized mice. In the YER yeast cells, E2, NP, BPA, GEN, and BP exhibited estrogenicity in a doseresponse manner, while TCDD did not. All the chemicals tested, except T, did not show androgenicity in the YAR yeast cell. The sensitivity of the yeast (YER) assay system to the estrogenic effect of NP was similar to that of the E-screen assay. NP was also estrogenic in the uterotrophic assay. However, in terms of convenience and costs, the yeast assay was superior to the E-screen assay or uterotrophic assay. These results suggest that the recombinant yeast assay can be used as a rapid tool for detecting chemicals with hormonal activities.

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