Pathology: Detection of initiation activity of 1,2-dimethylhydrazine in in vivo medium-term liver initiation assay system using 4-week-old rats without hepatocellular proliferative stimuli during the test chemical treatment period

• ASAOKA Yoshiji

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University Laboratory of Toxicology and Pharmacokinetics, Pharmaceutical Research Laboratories, Toray Industries, Inc.

• SAKAI Hiroki

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University Laboratory of Veterinary Pathology, Faculty of Applied Biological Sciences, Gifu University

• HIRATA Akihiro

  Division of Animal Experiment, Life Science Research Center, Gifu University

• SASAKI Jun

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University Department of Veterinary Pathology, Faculty of Agriculture, Veterinary Medicine, Iwate University

• GORYO Masanobu

  Laboratory of Toxicology and Pharmacokinetics, Pharmaceutical Research Laboratories, Toray Industries, Inc. Department of Veterinary Pathology, Faculty of Agriculture, Veterinary Medicine, Iwate University

• MIYAMOTO Yohei

  Laboratory of Toxicology and Pharmacokinetics, Pharmaceutical Research Laboratories, Toray Industries, Inc.

• YANAI Tokuma

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University Laboratory of Veterinary Pathology, Faculty of Applied Biological Sciences, Gifu University

• MASEGI Toshiaki

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University Laboratory of Veterinary Pathology, Faculty of Applied Biological Sciences, Gifu University

• OKADA Kosuke

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University Department of Veterinary Pathology, Faculty of Agriculture, Veterinary Medicine, Iwate University

書誌事項

タイトル別名

• Detection of Initiation Activity of 1,2-Dimethylhydrazine in in vivo Medium-Term Liver Initiation Assay Ssytem using 4-Week-Old Rats without Hepatocellular Proliferative Stimuli during the Test Chemical Treatment Period

抄録

We have developed an in vivo medium-term liver initiation assay system to detect initiation activities of chemicals on multi-organ carcinogenesis. However, cell proliferation stimuli during the test chemical treatment period, required in the previously used assay models using adult rats, are laborious; moreover, those cause decrease of hepatic metabolic enzymes and psychological and physical discomfort to animals resulting in inaccurate interpretation. Therefore, we investigated the utility of another in vivo medium-term liver initiation assay model using 4-week-old rats without the cell proliferation stimuli. In this study, we confirmed that 4-week-old and 4.5-week-old male rats have high hepatocyte proliferation activity and similar enzyme activities of hepatic Cytochrome P450 subtypes as compared with 8-week-old male rats. Next, the in vivo medium-term liver initiation assay model using 4-week-old rats without cell proliferation stimuli was evaluated for the detection of the initiation activity of 1,2-dimethylhydrazine (DMH), which is a well-known genotoxic carcinogen. Four-week-old rats were orally administered DMH (single dose, 4 or 16 mg/kg; or 4-day repeat, 1 or 4 mg/kg); subsequently, these rats were treated promotion treatment consisted of administration of 2-acetylaminofluorene and carbon tetrachloride. Four weeks after the first DMH administration, the glutathione S-transferase placental form (GST-P)-positive foci induced by DMH in the liver was measured immunohistochemically. The inductions of GST-P-positive foci in all DMH-treated groups were dose-dependent, duration-dependent and significantly higher than that in non-DMH-treated group. From these results, our assay model was detected the initiation activity of DMH simply, and would be useful to evaluate the carcinogenicity of chemicals.<br>

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ 72 (1), 43-53, 2010

  公益社団法人 日本獣医学会

キーワード

• 1,2-dimethylhydrazine (DMH)Introduction
• carcinogenesis
• GST-P-positive cell foci
• liver
• rat

詳細情報

• CRID: 1390282681404804480
• NII論文ID: 130000134508
• NII書誌ID: AA10796138
• DOI: 10.1292/jvms.09-0297
• ISSN: 13477439
• ISSN: 09167250
• NDL書誌ID: 10563671
• Web Site: http://id.ndl.go.jp/bib/10563671
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10563671
• Web Site: http://www.jstage.jst.go.jp/article/jvms/72/1/72_09-0297/_pdf
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
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