Short-term detection of gastric genotoxicity using the DNA double-strand break marker γ-H2AX

• Okabe Asako

  Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

• Kiriyama Yuka

  Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan Department of Diagnostic Pathology, Narita Memorial Hospital, 134 Haneihonmachi, Toyohashi, Aichi 441-8029, Japan

• Suzuki Shugo

  Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan

• Sakurai Kouhei

  Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

• Teramoto Atsushi

  Faculty of Radiological Technology, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

• Kato Hiroyuki

  Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan

• Naiki-Ito Aya

  Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan

• Tahara Sayumi

  Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

• Takahashi Satoru

  Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan

• Kuroda Makoto

  Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

• Sugioka Atsushi

  Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

• Tsukamoto Tetsuya

  Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

抄録

DNA damage caused by Helicobacter pylori infection and chronic inflammation or exposure to genotoxic agents is considered an important risk factor of gastric carcinogenesis. In this study, we have evaluated a short-term technique to detect DNA damage response to various chemical carcinogens; it involves visualization of Ser 139-phosphorylated histone H2AX (γ-H2AX) foci by immunohistochemistry and expression analysis of other genes by quantitative RT-PCR. Six-week-old male rats were intragastrically administered N-methyl-N-nitrosourea (MNU), 3,2’-dimethyl-4-aminobiphenyl (DMAB), dimethylnitrosamine (DMN), and 1,2- dimethylhydrazine (DMH) for 5 days/week for 4 weeks, using corn oil as a vehicle. Animals were sacrificed at day 28, and their stomachs were excised. γ-H2AX foci formation, indicating DNA double-strand breaks, was observed in the proliferative zone of both fundic and pyloric glands. The number of positive cells per gland was significantly high in pyloric glands in the MNU group and in fundic glands in the MNU and DMAB groups. A significant increase in p21waf1 mRNA level was observed in the DMN group compared with the control, which was in contrast to the decreasing tendency of the h2afx mRNA level in the MNU and DMN groups. Apoptotic cells positive for γ-H2AX pan or peripheral nuclear staining were observed on the surface layer of the fundic mucosa in the MNU group. The fundic pepsinogen a5 (pga5) mRNA level showed a significant decrease, indicating gland damage. The pyloric pepsinogen c mRNA level showed no change. In conclusion, γ-H2AX in combination with other gene expression analyses could be a useful biomarker in a short-term experiment on gastric chemical genotoxicity.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃ　Ｐａｔｈｏｌｏｇｙ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃ　Ｐａｔｈｏｌｏｇｙ 32 (2), 91-99, 2019

  日本毒性病理学会

キーワード

• stomach
• gastric cancer
• DNA double-strand break
• γ-H2AX
• p21
• pepsinogen

詳細情報

• CRID: 1390001288132186880
• NII論文ID: 130007636048
• NII書誌ID: AN10232280
• DOI: 10.1293/tox.2019-0007
• ISSN: 1881915X
• ISSN: 09149198
• NDL書誌ID: 029722450
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029722450
• Web Site: https://www.jstage.jst.go.jp/article/tox/32/2/32_2019-0007/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020003544
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
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