Concurrent administration of ascorbic acid enhances liver tumor-promoting activity of kojic acid in rats
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概要
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We previously found that administration of ascorbic acid (AA) enhances the liver tumor-promoting activity of kojic acid (KA) in mice. To examine the reproducibility of these results in rats and the underlying mechanism of this effect, we employed a two-stage liver carcinogenesis model using male F344 rats. Two weeks after initiation with diethylnitrosamine (DEN), the animals received a diet containing 2% KA and drinking water with or without 5,000 ppm AA for a period of 7 weeks. A DEN-alone group was also established as a control. One week after the commencement of the administration, the animals were subjected to two-thirds partial hepatectomy. At the end of the experiment, the livers were analyzed immunohistochemically, and the mRNA expression level and extent of lipid peroxidation were measured. AA treatment enhanced the KA-induced tumor-promoting activity in terms of the number and area of liver cell foci that were positive for glutathione-S-transferase placental form. AA coadministration increased the number of hepatocytes positive for proliferating cell nuclear antigen and inversely decreased the number of TUNEL-positive cells. However, the increased level of thiobarbituric acid reactive substances resulting from KA treatment was suppressed by coadministration of AA. Gene expression analyses using low-density microarrays and real-time RT-PCR showed that coadministration of AA resulted in upregulation of genes related to cell proliferation and downregulation of those involved in apoptosis and/or cell cycle arrest. These results indicate that the concerted effects of AA on cell proliferation and apoptosis/cell cycle arrest probably through its antioxidant activity are involved in this enhancement.
- 日本トキシコロジー学会の論文
- 2008-05-01
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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NISHIMURA Jihei
Laboratory of Veterinary Pathology, 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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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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Mitsumori K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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三森 国敏
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Yasuno Hironobu
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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Takabatake Masayoshi
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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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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Maita K
The Institute Of Environmental Toxicology:agrotox Inc.
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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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Yasuno Hironobu
Laboratory Of Veterinary Pathology 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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Shibutani Makoto
Division Of Pathology National Institute Of Health Sciences
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Takabatake Masayoshi
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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