• 한국환경성돌연변이발암원학회지
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• 제26권3호
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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.

• 한국환경성돌연변이발암원학회지
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• 제26권3호
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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.

• 대한의생명과학회지
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• 제26권2호
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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.

• Journal of Ginseng Research
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• 제30권1호
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• pp.8-14
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• 2006

본 연구는 랫드에서 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD)로 유도된 급성독성에 대한 홍삼유출액으로부터 분리한 조사포닌의 방어효과를 조사하기 위해 수행되었다. 40마리의 웅성 랫드를 4군으로 나누어 정상군에 대해서는 TCDD의 운반체를, TCDD 단독투여군 (TT)에게는 TCDD($5{\mu}g/ml$)와 생리식염수를 1회 복강주사하였다. 한편, 조사포닌 투여군 (RGE-CS20, RGE-CS40)은 조사포닌을 각각 20 및 40 mg/kg,b.w/day의 용량으로 TCDD 투여 1주 전부터 총 4 주간 복강주사하였다. TCDD 단독투여군의 체중은 TCDD투여 1주째부터 유의하게 감소한 반면, 조사포닌 투여군은 TCDD 단독투여군에 비해 완만하기는 하지만 유의하게 증가하여 체중감소가 억제되었다. 조사포닌 투여군은 TCDD독성에 의해 증가한 TG, TC, LDL, AST ALT, $Fe^{2+}$ 함량은 감소시켰고, TCDD 독성에 의해 감소된 glucose, amylase, LDH, CK 활성을 증가시켜 혈액 임상화학지수를 유의하게 개선시키는 것으로 나타났다. 이상의 결과로부터 홍삼유출액으로부터 분리한 조사포닌은 TCDD에 의해 주도된 체중감소와 장기 기능저하에 대해서 현저한 방어효과를 나타낸다는 사실을 알 수 있었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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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)

• 디지털융복합연구
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• 제11권4호
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• pp.339-350
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• 2013

홍삼 사포닌분획(SF)투여 시 TCDD(2,3,7,8-tetracholorodibenzo-${\rho}$-dioxin)투여(TT)에 의해 감소했던 웅성 기니피그의 체중과 간, 콩팥, 지라, 고환의 무게가 유의하게 증가하였다(p>0.01). SF투여 시 TCDD투여에 의해 감소했던 헤마토크릿 값, 적혈구 및 혈소판의 수, 아밀라아제 및 lactate dehydrogenase의 활성도, 요산, 총단백질 및 알부민의 양은 증가했고, 증가했던 백혈구의 수, 중성지질, 총콜레스테롤(TC), 혈당, 저밀도지단백질-콜레스테롤, 고밀도지단백질-콜레스테롤, 크레아티닌, 혈중 요소질소, 칼슘 및 인의 양과 creatinine kinase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase의 활성은 감소하였다. 그리고 적혈구, 백혈구, 혈소판, 혈당, TC, 칼슘 및 알부민을 제외한 모든 지표들은 통계학적 유의성을 보였다(p>0.01). 이상의 결과로부터 SF는 TCDD에 의해 유도된 기니피그의 급성독성을 완화시켜 주는 효과가 있음을 알 수 있었다.

• Journal of Microbiology and Biotechnology
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• 제10권3호
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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.