Suppressive effect of liver tumor-promoting activities in rats subjected to combined administration of phenobarbital and piperonyl butoxide
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- Morita Reiko
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University
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- Yafune Atsunori
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University
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- Shiraki Ayako
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University
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- Itahashi Megu
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University
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- Akane Hirotoshi
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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- Nakane Fumiyuki
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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- Suzuki Kazuhiko
- Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology
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- Shibutani Makoto
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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- Mitsumori Kunitoshi
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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抄録
Phenobarbital (PB) is a cytochrome P450 (CYP) 2B inducer, and piperonyl butoxide (PBO) is a CYP1A/2B inducer. These inducers have liver tumor-promoting effects in rats. In this study, we performed a rat two-stage liver carcinogenesis bioassay to examine the tumor-promoting effect of PB and PBO co-administration. Male rats received an intraperitoneal injection of N-diethylnitrosamine (DEN) for initiation. Two weeks after DEN administration, rats were given PB (60 or 120 ppm in drinking water), PBO (1,250 or 2,500 ppm in diet) or 60 ppm PB+1,250 ppm PBO for 6 weeks. One week after the PB/PBO treatment, all rats were subjected to a two-thirds partial hepatectomy. To evaluate the effect of the combined administration, we used two statistical additive models. In the isoadditive model, the average values of the area of GST-P positive foci in the PB+PBO group were significantly lower than those in the High PB or High PBO groups. In the heteroadditive model, the net values of Cyp1a1 mRNA level and microsomal reactive oxygen species (ROS) production in the PB+PBO group were significantly lower than the sum of those in the Low PB or Low PBO groups. On the contrary, there was no interactive effect in the PCNA-positive hepatocyte ratio, mRNA levels of Cyp2b1/2, Gstm3, Gpx2 and Nqo1, and the level of thiobarbituric acid-reactive substances in the PB+PBO group. These results suggest that PB and PBO co-administration causes suppressive effects in liver tumor-promoting activity in rats resulting from inhibited microsomal ROS production because of suppression of CYP1A induction.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 38 (5), 679-688, 2013
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390282679881103104
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- NII論文ID
- 10031191726
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC3sXhslyitb3J
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024933924
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- PubMed
- 24025784
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可