Search for in vivo early prediction markers of carcinogenicity based on the induction mechanism of karyomegaly

2012 Fiscal Year Final Research Report

• Project/Area Number: 22380163
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: SHIBUTANI Makoto 東京農工大学, 大学院・農学研究院, 教授 (20311392)
• Co-Investigator(Kenkyū-buntansha): MITSUMORI Kunitoshi 東京農工大学, 大学院・農学研究院, 教授 (10239296)
• Project Period (FY): 2010 – 2012
• Keywords: がん / 病理学 / 発がん性評価 / 短期予測 / 巨大核 / 細胞増殖活性 / 細胞周期 / アポトーシス

Research Abstract

There are carcinogens that can induce karyomegaly reflecting cell cycle aberration in carcinogenic target cells. In this study, we found that carcinogens evoking facilitation of cell proliferation increased apoptosis and M phase-disrupting cells in the carcinogenic target organs after28-day treatment in rats, and thus, we obtained candidates for early prediction markers ofcarcinogenicity. We also found that tumor promotion with karyomegaly-inducing hepatocarcinogens may cause disruption of cell cycle regulation through epigenetic gene modification of p16^Ink4a in the carcinogenic process from the early stage.

Research Products

• [Journal Article] Involvement of multiple cell cycle aberrations in early preneoplastic liver cell lesions by tumor promotion with thioacetamide in a two-stage rat hepatocarcinogenesis model (2012)
  • Author(s): Kimura, M., Fujii, Y., Yamamoto, R., Yafune, A., Hayashi, S-M., Suzuki, K., Shibutani, M
  • Journal Title: Exp. Toxicol. Pathol Volume: (印刷中)
  • DOI: doi:10.1016/j.etp.2013.01.012.
  • Peer Reviewed
• [Journal Article] Fluctuations in cell proliferation, apoptosis, and cell cycle regulation at the early stage of tumor promotion in rat two-stage carcinogenesis models (2012)
  • Author(s): Taniai, E., Yafune, A., Kimura, M., Morita, R., Nakane, F., Suzuki, K., Mitsumori, K., Shibutani, M
  • Journal Title: J. Toxicol. Sci Volume: 37(6) Pages: 1113-1126
  • URL: http://dx.doi.org/10.2131/jts.37.1113.
  • Peer Reviewed
• [Journal Article] Aberrant activation of ubiquitin D at G_2 phase and apoptosis by carcinogens that evoke cell proliferation after 28-day administration in rats (2012)
  • Author(s): Taniai, E., Yafune, A., Hayashi, H., Itahashi, M., Hara-Kudo, Y., Suzuki, K., Mitsumori, K., Shibutani, M
  • Journal Title: J. Toxicol. Sci. Volume: 37(6) Pages: 1093-1111
  • URL: http://dx.doi.org/10.2131/jts.37.1093.
  • Peer Reviewed
• [Journal Article] Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16^Ink4a) in early-stage liver tumor-promotion facilitating iver cell regeneration in rats (2012)
  • Author(s): Tsuchiya, T., Wang, L., Yafune, A., Kimura, M., Ohishi, T., Suzuki, K., Mitsumori, K., Shibutani, M
  • Journal Title: Toxicology Volume: 299(2-3) Pages: 146-154
  • DOI: doi:10.1016/j.tox.2012.05.018.
  • Peer Reviewed
• [Journal Article] Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days-Relationship between cell cycle aberration and carcinogenesis (2012)
  • Author(s): Taniai, E., Hayashi, H., Yafune, A., Watanabe, M., Akane, H., Suzuki, K., Mitsumori, K., Shibutani M
  • Journal Title: Arch. Toxicol Volume: 86(9) Pages: 1453-1464
  • DOI: doi:10.1007/s00204-012-0829-z.
  • Peer Reviewed
• [Presentation] ラット二段階発がんモデルを用いた発がんプロモーション過程早期における細胞増殖、アポトーシス及び細胞周期関連分子の局在変化 (2013)
  • Author(s): 谷合枝里子、八舟宏典、盛田怜子、板橋恵、鈴木和彦、三森国敏、渋谷淳
  • Organizer: 第29回日本毒性病理学会学術集会,第29回日本毒性病理学会学術集会講演要旨集
  • Place of Presentation: つくば
  • Year and Date: 20130131-0201
• [Presentation] チオアセタミドのラット肝発がん促進時に誘発される細胞周期以上に対する酸化性ストレスの関与 (2012)
  • Author(s): 木村真之、藤井雄太、山本龍一、谷合枝里子、八舟宏典、林新茂、鈴木和彦、三森 国敏、渋谷淳
  • Organizer: 第39回日本毒性学会学術集会,第39回日本毒性学会学術集会講演要旨集
  • Place of Presentation: 仙台
  • Year and Date: 20120717-19
• [Presentation] 発がん標的性の異なる発がん物質のラットに対する28日間投与時の各標的臓器でのラット腎発がん物質反応指標の変動 (2012)
  • Author(s): 谷合枝里子、八舟宏典、盛田怜子、赤根弘敏、林仁美、鈴木和彦、三森国敏、渋谷淳
  • Organizer: 第28回日本毒性病理学会学術集会,第28回日本毒性病理学会学術集会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 20120202-03
• [Presentation] シンポジウム「オクラトキシンAのリスク評価最前線」、オクラトキシンAの毒性・発がん性に関する現在までの情報 (2012)
  • Author(s): 渋谷淳
  • Organizer: 第70回マイコトキシン学会.第70回マイコトキシン学会要旨集
  • Place of Presentation: 東京
  • Year and Date: 2012-01-06
• [Presentation] Search for rapid detection markers of renal carcinogens based on the karyomegaly-induction mechanism in rats (2011)
  • Author(s): Eriko Taniai, Hitomi Hayashi, Atsunori Yafune, Kazuhiko Suzuki, Kunitoshi Mitsumori, Makoto Shibutani
  • Organizer: 70^<th> Annual Meeting of the Japanese Cancer Association. Proceedings
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-05
• [Presentation] ラットthioacetamide(TAA)肝発がん促進過程で形成される前がん病変における細胞周期破綻の様式 (2011)
  • Author(s): 土屋卓磨、谷合枝里子、八舟宏典、白木彩子、北条友理、鈴木和彦、三森国敏、渋谷淳
  • Organizer: 第152回日本獣医学会学術集会,第152回日本獣医学会学術集会講演要旨集
  • Place of Presentation: 大阪
  • Year and Date: 20110919-21
• [Presentation] Search for in vivo rapid screening markers of renal carcinogens based on the analysis ofinduction mechanism of karyomegaly (2011)
  • Author(s): Eriko Taniai, Hitomi Hayashi, Atsunori Yafune, Liyun Wang, Kazuhiko Suzuki, Kunitoshi Mitsumori, Makoto Shibutani
  • Organizer: 9thEuropean Congress of Toxicologic Pathology of the European Society of Toxicologic Pathology
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 20110907-10
• [Presentation] 腎発がん物質の28日間短期投与時でのラットの腎尿細管領域の細胞増殖性を考慮した細胞周期関連分子の発現解析 (2011)
  • Author(s): 谷合枝里子、中村憲彦、林仁美、嶋本敬介、WangLiyun、大石巧、剣持明、小西良子、鈴木和彦、三森国敏、渋谷淳
  • Organizer: 第38回日本トキシコロジー学会学術集会,第38回日本トキシコロジー学会学術集会講演要旨集
  • Place of Presentation: 横浜
  • Year and Date: 20110711-13
• [Presentation] 巨大核出現を伴う腎発がん物質の28日間投与ラットの腎尿細管における細胞周期関連分子の発現変化、文部科学省科学研究費補助金がん研究分野の特性等を踏まえた支援活動 (2011)
  • Author(s): 谷合枝里子、土屋卓磨、黒岩有一、林仁美、鈴木和彦、三森国敏、渋谷淳
  • Organizer: 個体レベルでのがん研究支援活動
  • Place of Presentation: 大津
  • Year and Date: 20110203-04
• [Presentation] 巨大核出現を伴う腎発がん物質の28日間投与時でのラット腎尿細管における細胞周期関連分子の発現挙動 (2011)
  • Author(s): 谷合枝里子、土屋卓磨、黒岩有一、林仁美、鈴木和彦、三森国敏、渋谷淳
  • Organizer: 第27回日本毒性病理学会学術集会,第27回日本毒性病理学会学術集会講演要旨集
  • Place of Presentation: 大阪
  • Year and Date: 20110127-28