The Effects of D-galactosamine- or Carbon Tetrachloride-Induced Regeneration on Induction of Rat Liver Cell Foci in a Model for Detection of Initiation Activities of Chemicals
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概要
- 論文の詳細を見る
The effects of D-galactosamine (D-gal) and carbon tetrachloride (CCl4) administration on induction of liver cell proliferation in a medium term liver bioassay for detection of initiation activity of 1,2-dimethylhydrazine (DMH) were investigated with special emphasis on kinetics of cell proliferation and cytochrome P450 (CYP) expression. In experiment I, fluctuation of cell proliferation and CYP 2E1, which is one of the enzymes involved in bioactivation DMH to ultimate form, levels of liver cells after D-gal administration (4000 mg/kg, i.g.) or CCl4 administration (1 ml/kg, i.g.) was analyzed by bromodeoxyuridine labeling and western blotting, respectively. In experiment II, induction of glutathione S-transferase placental form (GST-P)-positive foci by DMH in a model for detection of initiation activities using D-gal or CCl4 administration as a toxicity-regeneration dependent proliferative stimulus was evaluated. Although high BrdU labeling indices continued from 36 h to 72 h after D-gal and CCl4 treatment, cell proliferation after intragastric D-gal administration was very low compared with the CCl4 case. Decrease of CYP 2E1 apoprotein content in the microsomes was slight after D-gal administration, whereas decrease up to about 40% of the control level was evident from 12 h until 60 h after CCl4. When the carcinogen was injected 60 h after D-gal administration, there was appreciable increase in the area and numbers of GST-P positive foci, similar to the case with CCl4 administration. Sensitivities for detection of initiation activity with intragastric D-gal or CCl4 administration were equal, despite the kinetics of cell proliferation and CYP 2E1 being very different. With CCl4 administration, initiation depended on fluctuation of CYP 2E1, reversibly in intragastric D-gal treatment, initiation depended on cell kinetics.
- 日本毒性病理学会の論文
- 2002-03-25
著者
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Tsukamoto T
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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HIRATA Akihiro
Division of Oncological Pathology, Aichi Cancer Center Research Institute
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YANAI Tokuma
Department of Veterinary Pathology, Gifu University
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MASEGI Toshiaki
Department of Veterinary Pathology, Gifu University
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IIDAKA Takeshi
Division of Oncological Pathology, Aichi Cancer Center Research Institute
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SHIRAI Norimitsu
Division of Oncological Pathology, Aichi Cancer Center Research Institute
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HIRATA Akihiro
Department of Veterinary Pathology, Gifu University
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TSUKAMOTO Tetsuya
Laboratory of Pathology, Aichi Cancer Center Research Institute
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TATEMATSU Masae
Laboratory of Pathology, Aichi Cancer Center Research Institute
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SHIRAI Norimitsu
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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SAKAI Hiroki
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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INAGAMI Atsushi
Department of Veterinary Pathology, Gifu University
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KOBAYASHI Kiyoshi
Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals. Inc.
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DEGAWA Masakuni
Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
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IIDAKA Takeshi
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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Iidaka Takeshi
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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坂井 宏明
帯広畜産大学畜産学部獣医学科家畜内科学教室
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Yanai T
Department Of Veterinary Pathology Gifu University
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Totsuka Yukari
大阪府立大学先端科学イノベーションセンター 遺伝子環境科学研究室
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Totsuka Y
Cancer Prevention Basic Research Project
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Tatematsu M
愛知県がんセンター研究所 腫瘍病理学部
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Yanai Tokuma
Department Of Veterinary Pathology Faculty Of Agriculture Gifu University
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Yamachika Takasuke
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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Kobayashi K
Toxicology Laboratory Research Center Mitsubishi-tokyo Pharmaceuticals. Inc.
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Imai Toshio
Laboratory Of Pathology Aichi Cancer Center Research Institute
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Takaoka Masaya
Medicinal Safety Research Laboratories Daiichi-sankyo Co. Ltd.
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Tatematsu Masae
Laboratory Of Pathology Aichi Cancer Center Research Institute
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Shirai Norimitsu
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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Inagami Atsushi
Department Of Veterinary Pathology Gifu University
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Tsukamoto Takahisa
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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Sakai Hiroki
Laboratory Of Biological Chemistry Department Of Chemistry Faculty Of Science Hokkaido University
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Degawa Masakuni
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Tohoku University
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Degawa Masakuni
Department Of Molecular Toxicology School Of Pharmaceutical Sciences University Of Shizuoka
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Masegi Toshiaki
Department Of Veterinary Pathology Faculty Of Agriculture Gifu University
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Tsukamoto Tetsuya
Laboratory Of Pathology Aichi Cancer Center Research Institute
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Tsukamoto T
Department Of Public Health Osaka City University Graduate School Of Medicine
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Totsuka Yukari
国立がん研究センター研究所 発がんシステム研究分野
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Kobayashi Kiyoshi
Toxicology Laboratory Mitsubishi Pharma Co.
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Kobayashi Kiyoshi
Toxicology Laboratory Yokohama Research Center Mitsubishi Chemical Corporation
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Masegi Toshiaki
Department Of Gastroenterology And Metabolism Nagoya City University Graduate School Of Medical Scie
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Makita Takashi
Medicinal Safety Research Laboratories Daiichi Sankyo Co. Ltd.:department Of Veterinary Pathology Gr
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Imai T
Human Genome Ctr.
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YANAI Tokuma
Department of Pathogenetic Veterinary Sciences, United Graduate School of Veterinary Sciences, Gifu University, 1–1 Yanagido, Gifu 501–1193, Japan
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HIRATA Akihiro
Department of Veterinary Pathology, Faculty of Agriculture, Gifu University
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Tatematsu Masae
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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Tsukamoto Tetsuya
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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