Molecular Analysis on the Possible Mechanism of β-Naphthoflavone-Induced Hepatocarcinogenesis in Rats
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概要
- 論文の詳細を見る
It has been speculated that oxidative stress is involved in the liver tumor-promoting effect of β-naphthoflavone (BNF; 5,6-benzoflavone) in rats, because of its strong induction of cytochrome P450 (CYP) 1A enzymes. In order to clarify the mechanism of liver tumor promoting effects of BNF, male F344 rats were initiated with a single intraperitoneal injection of 200 mg/kg diethylnitrosamine (DEN), and fed diet containing 2% of BNF for 6 weeks staring 2 weeks after injection. Two/third partial hepatectomy was perfomed at Week 3 after the treatment of BNF. Low-density Rat Toxicology & Drug Resistance Microarray and quantitative analyses of mRNA expressions of the selected genes using real-time reverse transcription (RT) -PCR were carried out on total RNAs extracted from the livers of F344 rats. Collected liver tissues were subjected to light microscopic examinations (hematoxylin and eosin staining), immunohistochemistries of proliferating cell nuclear antigen (PCNA), glutathione S-transferase placental form (GST-P) and CYP1A1, and Schmorl staining to identify lipofuscin. Gene expression analysis showed that 7 genes (CYP1A1, CYP1A2, CYP1B1, Gstm2 (GST mu2), Gstm3, glutathione peroxidase (Gpx)2 and NAD(P)H dehydrogenase, quinone 1(Nqo1)) were up-regulated (> 1.5 fold), and 4 genes (8-oxoguanine DNA glycosylase (Ogg1), Gpx1, peroxiredoxin (Prdx) 1 and P450 oxidoreductase (Por)) were down-regulated (< 0.67 fold) in the DEN + BNF group rats as compared with the DEN alone group. In immunohistochemical analyses, the numbers of foci positive for GST-P, the rate of PCNA-positive cells, and the rate of CYP1A1-positive cells were significantly increased in the DEN + BNF group, as compared to the corresponding control. Furthermore, deposition of lipofuscin, positive for Schmorl staining, was moderately increased in the DEN + BNF group. These results confirm the possibility that oxidative stress is involved in the liver tumor-promoting effect of BNF in rats.
- 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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DEWA Yasuaki
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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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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TAKAHASHI Miwa
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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Dewa Yasuaki
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Dewa Yasuaki
東京農工大学 獣医病理学
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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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Takahashi Miwa
Laboratory Of Veterinary Pathology Faculty Of Agriculture Tokyo University Of Agriculture And Techno
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