Induction of cell proliferation in the rat liver by the short-term administration of ethyl <i>tertiary</i>-butyl ether

• Kakehashi Anna

  Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

• Hagiwara Akihiro

  DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan

• Imai Norio

  DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan

• Wei Min

  Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

• Fukushima Shoji

  Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0011, Japan

• Wanibuchi Hideki

  Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

Bibliographic Information

Other Title

• Induction of cell proliferation in the rat liver by the short-term administration of ethyl tertiary-butyl ether

Abstract

In the present study, in continuation of our previous experiment in order to investigate the mode of action (MOA) of ethyl tertiary-butyl ether (ETBE) hepatotumorigenicity in rats, we aimed to examine alterations in cell proliferation, that are induced by short-term administration of ETBE. F344 rats were administered ETBE at doses of 0, and 1,000 mg/kg body weight twice a day by gavage for 3, 10, 17 and 28 days. It was found that the previously observed significant increase of P450 total content and hydroxyl radical levels after 7 days of ETBE administration, and 8-OHdG formation at day 14, accompanied by accumulation of CYP2B1/2B2, CYP3A1/3A2, CYP2C6, CYP2E1 and CYP1A1 and downregulation of DNA oxoguanine glycosylase 1, was preceded by induction of cell proliferation at day 3. Furthermore, we observed an increase in regenerative cell proliferation as a result of ETBE treatment at day 28, followed by induction of cell cycle arrest and apoptosis by day 14. These results indicated that short-term administration of ETBE led to a significant early increase in cell proliferation activity associated with induction of oxidative stress, and to a regenerative cell proliferation as an adaptive response, which could contribute to the hepatotumorigenicity of ETBE in rats.

Journal

• Journal of Toxicologic Pathology

  Journal of Toxicologic Pathology 28 (1), 27-32, 2015

  JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

Keywords

• ethyl <i>tertiary</i>-butyl ether
• cell proliferation
• oxidative stress
• mode of action

Details

• CRID: 1390282679393204096
• NII Article ID: 130004842605
• NII Book ID: AN10232280
• DOI: 10.1293/tox.2014-0056
• ISSN: 1881915X
• ISSN: 09149198
• NDL BIB ID: 026103192
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026103192
• Web Site: https://www.jstage.jst.go.jp/article/tox/28/1/28_2014-0056/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015345210
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed