Liver tumor promoting effect of etofenprox in rats and its possible mechanism of action

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To investigate the liver tumor-promoting effects of etofenprox (ETF), a pyrethroid-like insecticide, 6 week-old male F344 rats were given an intraperitoneal injection of <i>N</i>-diethylnitrosamine (DEN). After 2 weeks from the DEN treatment, 12 rats per group received a powdered diet containing 0, 0.25, 0.50, or 1.0% ETF for 8 weeks. At the time of 2nd week of ETF administration, all animals were subjected to two-thirds partial hepatectomy (PH). One rat per group except for the 0.25% ETF group died due to surgical operation of PH. The number and area of glutathione S-transferase placental form (GST-P) positive foci significantly increased in the livers of DEN-initiated rats given 0.50% and 1.0% ETF compared with the DEN-alone group. Quantitative real-time RT-PCR analysis revealed that the mRNA expression of phase I enzymes <i>Cyp2b1/2</i>, phase II enzymes such as <i>Akr7a3</i>, <i>Gsta5</i>, <i>Ugt1a6</i>, <i>Nqo1</i> significantly increased in the DEN+ETF groups. The immunohistochemistry showed the translocation of CAR from the cytoplasm to the nuclei of hepatocytes in the ETF-treated groups. Reactive oxygen species (ROS) production increased in microsomes isolated from the livers of ETF-treated rats, and thiobarbituric acid-reactive substances (TBARS) levels and 8- hydroxy-2-deoxyguanosine (8-OHdG) content significantly increased in all of the ETF-treated groups and DEN+1.0% ETF group, respectively. The results of the present study indicate that ETF has a liver tumor-promoting activity in rats, and suggest that ETF activates the constitutive active/androstane receptor (CAR) and enhances microsomal ROS production, resulting in the upregulation of Nrf2 gene batteries; such an oxidative stress subsequently induces liver tumor-promoting effects by increased cellular proliferation.

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  • Journal of toxicological sciences

    Journal of toxicological sciences 37(2), 297-306, 2012-04-01

    The Japanese Society of Toxicology

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各種コード

  • NII論文ID(NAID)
    10030126650
  • NII書誌ID(NCID)
    AN00002808
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    03881350
  • NDL 記事登録ID
    023674363
  • NDL 請求記号
    Z19-1022
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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