The effect of 2,3,7,8-Tetrafluorodibenzo-p-dioxin on Dioxin Toxicity

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  • Takeda Tomoki
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Hitomi Masaya
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Yamada Hideyuki
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Ishii Yuji
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University

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Other Title
  • 2,3,7,8-Tetrafluorodibenzo-p-dioxinのダイオキシン毒性に対する拮抗作用
  • 2,3,7,8-Tetrafluorodibenzo-p-dioxin ノ ダイオキシン ドクセイ ニ タイスル キッコウ サヨウ

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Abstract

Maternal exposure to dioxin produces a number of developmental toxicity, such as growth retardation and defects in sexual dimorphic behaviors in offspring. Our previous studies have found that the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic congener of dioxins, are due to a reduction in the pituitary expression of growth hormone (GH) and luteinizing hormone (LH) during the fetal period, via activation of the aryl hydrocarbon receptor (AHR). In this study, we examined whether 2,3,7,8-tetrafluorodibenzo-p-dioxin (TFDD), the analog of TCDD in which chlorine atoms are replaced with fluorine atoms, can antagonize dioxin toxicity. In T47D cells, TCDD (0.5 nM) dramatically increased the activity and expression of cytochrome P450 1A1 (CYP1A1), a representative gene induced by AHR activation. However, TFDD co-treatment suppressed the induction in a dose-dependent manner. Its median effective dose (ED50) was estimated as 45.9 nM. In contrast, although exposing 1 mg/kg TCDD to pregnant rats attenuated the expression of LHb and GH mRNA and induced the expression of CYP1A1 mRNA in the male fetal pituitary, daily oral administration of TFDD (1 mg/kg/day) to the TCDD-exposed dams did not have any suppressive effects. These results suggest that maternal treatment with TFDD, even at 1,000 times the dose of TCDD, cannot block dioxin-produced developmental toxicity in fetuses.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 110 (2), 122-127, 2019-06-25

    Fukuoka Medical Association

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