Reactive Oxygen Species Are Possibly Involved in the Mechanism of Flumequine-Induced Hepatocarcinogenesis in Mice
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概要
- 論文の詳細を見る
Flumequine (FL), a quinolone antibiotic used for veterinary treatment of bacterial infections, has been reported to exert hepatocarcinogenicity in mice, and oxidative stress has been considered as a possible underlying mechanism. To elucidate the tumor-promoting mechanism of FL in mice, we employed a two-stage liver carcinogenesis model. Livers from mice were subjected to histopathological examinations, histochemistry for γ-glutamyltranspeptidase (GGT), and immunohistochemistry for PCNA. In addition, gene expression analyses were performed using low-density cDNA microarrays for mouse stress and toxicity and drug metabolism, and quantitative real-time RT-PCR analyses. On histopathological examinations, centrilobular hypertrophy, vacuolation, and mitotic figures of liver cells were observed in animals receiving FL, with or without DEN-initiation. The number of GGT- and PCNA-positive hepatocytes in the DEN+FL group was significantly higher than that in the DEN alone group. In the gene expression analysis, animals of the DEN+FL group showed significant up-regulations of oxidative and metabolic stress related genes, such as glutathione S-transferase (Gst) α2, Gstμ2, microsomal epoxide hydrolase (Ephx1), NAD(P)H:quinone oxidoreductase 1 (Nqo1), γ-glutamylcysteine synthetase heavy subunit (γGCSh), and NF-E2 related factor 2 (Nrf2), as well as extracellular signal regulated kinase 5 (ERK5) and c-Jun, as compared to the DEN alone group. Additionally, the in vitro measurement of reactive oxygen species (ROS) generated in the mouse liver microsomes showed a significant increase of ROS production induced by FL. These results support our previous hypothesis that oxidative stress plays an important role in FL-induced hepatocarcinogenesis in mice.
- 日本毒性病理学会の論文
- 2007-03-30
著者
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JIN Meilan
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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NISHIMURA Jihei
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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Mitsumori Kunitoshi
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Mitsumori Kunitoshi
東京大学医科学研究所 癌細胞シグナル分野
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Mitsumori Kunitoshi
国立医薬品食品衛生研究所 病理部
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MOTO Mitsuyoshi
Laboratory of Veterinary of Pathology, Tokyo University of Agriculture and Technology
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Mitsumori K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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TAKAHASHI Miwa
Division of Pathology, National Institute of Health Sciences
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Muguruma Masako
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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KENMOCHI Yusuke
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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KOHNO Taichi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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YOKOUCHI Yusuke
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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Moto Mitsuyoshi
東京農工大学 獣医病理学
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Moto Mitsuyoshi
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Muguruma Masako
東京農工大学 獣医病理学
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Muguruma Masako
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Mitsumori Kunitoshi
Department Of Pathology National Institute Of Health Sciences
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Mitsumori Kunitoshi
Laboratory Of Veterinary Pathology Division Of Animal Science Institute Of Symbiotic Science And Tec
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Jin Meilan
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Kono Taichi
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Takahashi Miwa
Division Of Pathology National Institute Of Health Sciences
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Yokouchi Yusuke
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Kenmochi Yusuke
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Matsumoto K
Kyushu Univ. Fukuoka Jpn
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Matsumoto K
Drug Safety Research Laboratories Pharmaceutical Research Division Takeda Chemical Industries Ltd.:l
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三森 国敏
Division Of Pathology National Institute Of Health Sciences
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Matsumoto K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Nishimura Jihei
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Nishimura Jihei
Laboratory Of Applied Physiology Faculty Of Agriculture Kobe University Graduate School Of Science A
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Takahashi Miwa
Laboratory Of Veterinary Pathology Faculty Of Agriculture Tokyo University Of Agriculture And Techno
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