Phenoxy계 화합물의 내분비장애작용 검색 및 기전연구

김현정; 김원대; 권택헌; 김동현; 박영인; 동미숙

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자료유형: 학술저널

저자정보: 김현정 김원대 권택헌 김동현 박영인 동미숙

저널정보: 한국독성학회 Toxicological Research Journal of Toxicology and Public Health Vol.18 No.4

발행연도: 2002.12

수록면: 331 - 339 (9page)

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Phenoxy compounds, 2,4-Dichlorophenol acetoxy acid (2,4-D) and 2,4-dichlorophenol (DCP), are widely used as a hormonal herbicide and intermediate for pesticide manufacturing, respectively. In order to assess the potential of these compounds as endocrine disruptors, we studied the androgenicity of them using in vivo and in vitro androgenicity assay system. Administration of 2,4-D (50mg/kg/day, p.o.) or DCP (100mg/kg/day, p.o.) to rats caused an increase in the tissue weight of ventral prostate, Cowpers gland and glands penis. These increase of androgen-dependent tissues were additively potentiated when rats were simultaneously treated with low dose of testosterone (1g/kg, s.c.). 2,4-D increased about 350% of the luciferase activity in the PC cells transiently cotransfected phAR and pMMTV-Luc at concentration of 10^(-9)M. In 2,4-D or DCP-treated castrated rats, testosterone 6β-hydroxylase activity was not significantly modulated even when rats were co-treated with testoseterone. In vitro incubation of 2,4-D and DCP with microsomes at 50μM inhibited testosterone 6β-hydroxylase activity about 27% and 66% in rat liver microsomes, about 44% and 54% in human liver microsomes and about 50% and 45% in recombinant CYP3A4 system, respectively. The amounts of total testosterone metabolites were reduced about 33% and 75% in rat liver microsomes, 69% and 73% in human liver microsomes and 54% and 64% in recombinant CYP3A4 by 2,4-D or DCP, respectively. Therefore, the additive androgenic effect of 2,4-D or DCP by the co-administration of the low dose of testosterone may be due to the increased plasma level of testosterone by inhibiting the cytochrome P450-mediated metabolism of testosterone. These results collectively suggested that 2,4-D and DCP may act as androgenic endocrine disruptor by binding to the androgen receptor as well as by inhibiting the metabolism of testosterone.

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주요연구분야 의약학 > 의학 일반 의약학 > 기초의학 > 예방의학·직업환경의학

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소속기관 한국독성학회