The Effects of Allyl Alcohol-induced Cell Proliferation for Detection of Initiation Activities of Chemicals in Rat Liver
スポンサーリンク
概要
- 論文の詳細を見る
The effect of allyl alcohol (AA) administration on the induction of glutathione S-transferase placental form (GST-P) positive foci in medium term liver bioassay was investigated for the detection of initiation activities. In experiment I, the cell kinetics of rat liver after AA administration (0.1 ml/kg, i.g.) was analyzed by the 5-bromo-2-deoxyuridine (BrdU) labeling method. Cytochrome P450 (CYP) 2E1 protein, which is involved in the bioactivation of 1,2-dimethylhydrazine (DMH), was quantificated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and the immunohistochemical localization of CYP2E1 was also examined. In experiment II, the induction of GST-P positive foci by DMH was evaluated in a modified in vivo five-weeks initiation assay model using AA treatment to induce cell proliferation. AA induced periportal necrosis and led to regenerative proliferation. High BrdU labeling indices were observed from 24 h to 48 h (5-6%). CYP2E1 protein contents decreased transiently to approximately 40% of control after AA administration, but subsequently recovered to the control level. Immunohistochemically, CYP2E1 was localized in the centrilobular area each time, and the staining pattern was constant. The numbers and areas of GST-P positive foci were highly induced in the animals given DMH at 12 h after AA administration, compared to before the high BrdU labeling term. There was a correlation between the kinetics of cell proliferation and the induction of GST-P positive foci. Although CYP2E1 decreased after AA treatment, it is likely that the enzyme remained enough to metabolize DMH. These results suggest that AA-induced cell proliferation is an effective proliferative stimulus in medium-term initiation assay.
- 日本毒性病理学会の論文
- 2002-06-30
著者
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今井 敏夫
Drug Safety & Disposition Research Laboratories Eisai Co. Ltd.
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Tsukamoto T
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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SAKAI Hiroki
Department of Veterinary Pathology, Gifu University
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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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YAMAMOTO Masami
Laboratory of Pathology, Aichi Cancer Center Research Institute
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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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OKAMURA Miwa
Department of Veterinary Pathology, Gifu University
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TAKAHASHI Naofumi
Department of Veterinary Pathology, Gifu University
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INAGAMI Atsushi
Developmental Safety Assessment Research Drug & Disposition Research Laboratories Eisai Co., Ltd.
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SHIRAI Norimitsu
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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IIDAKA Takashi
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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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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Okamura Miwa
Department Of Veterinary Pathology Gifu University
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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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Tsukamoto Tetsuya
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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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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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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Tsukamoto Takahisa
First Department Of Oral And Maxillofacial Surgery School Of Dentistry
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Inagami Atsushi
Department Of Veterinary Pathology Gifu University
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Yamamoto M
Aichi Cancer Center Research Institute
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Tsukamoto Takahisa
Division Of Oncological Pathology Aichi Cancer Center Research Institute
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Masegi Toshiaki
Department Of Veterinary Pathology Faculty Of Agriculture Gifu University
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Takahashi Naofumi
Department Of Veterinary Pathology 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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Masegi Toshiaki
Department Of Gastroenterology And Metabolism Nagoya City University Graduate School Of Medical Scie
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Sakai Hiroki
Department Of Food Science Niigata University Of Pharmacy And Applied Life Sciences
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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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Yamamoto Masami
Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute
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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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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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