Induction of Genomic Instability Induced by Chromosome Mis-segregation and the Implication on Carcinogenesis

• Project/Area Number: 19510054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tohoku University
• Principal Investigator: NUNOSHIBA Tatsuo Tohoku University, 大学院・生命科学研究科, 准教授 (10270802)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Kazuo 東北大学, 大学院・生命科学研究科, 教授 (20093536)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 放射線生物影響 / ゲノム安定性 / 染色体不均等分配 / 非変異発がん物質 / LOH / phenyl hydroquinone / morphogenesis checkpoint / 染色体異数化 / Aneuploidy / 細胞周期 / 細胞がん化 / 出芽酵母 / 非変異原性発がん物質

Research Abstract

非変異発がん物質である輸入柑橘類の防カビ剤o-phenyl phenolの代謝物、phenyl hydroquinone (PHQ)をモデル物質とし、細胞周期と染色体分配機構への影響を検討した。その結果、酵母ではPHQがHog1-Swe1 checkpointを活性化しG2/Mの境界で細胞周期を停止させることが染色体異数化誘発に必要であること、ヒト培養細胞でもPHQが染色体数の異常を誘発することが確認できた。

Research Products

• [Journal Article] Induction of mitosis delay, apoptosis and aneuploidy in human cells by phenyl hydroquinone (2009)
  • Author(s): Imai M, Matsuno R, Komura J, Ono T, Yamamoto K.
  • Journal Title: an Ames test-negative carcinogen, Genes Genet Systems (in press)
  • Peer Reviewed
• [Journal Article] Phenyl hydroquinone, an Ames test-negative carcinogen (2008)
  • Author(s): Yamamoto A, Nunoshiba T, Umezu K, Enomoto T, Yamamoto Y
  • Journal Title: induces Hog1-dependent stress response signaling FEBS, J 275(22) Pages: 5733-5744
  • Peer Reviewed
• [Journal Article] UVA1 genotoxicity is mediated not by oxidative damage but by cyclobutane pyrimidine dimers in normal mouse skin (2008)
  • Author(s): Ikehata H, Kawai K, Komura J, Sakatsume K, Wang L, Imai M, Higashi S, Nikaido O, Yamamoto K, Hieda K, Watanabe M, Kasai H, Ono T.
  • Journal Title: J Invest Dermatol 128 Pages: 2289-2296
  • NAID: 120006576050
  • Peer Reviewed
• [Journal Article] Phenyl hydroquinone, an Ames test-negative carcinogen, induces Hogl-dependent stress response signaling (2008)
  • Author(s): Ayumi Yamamoto
  • Journal Title: FEBS J 275(22) Pages: 5733-5744
  • Peer Reviewed
• [Journal Article] Framesshift mutations produced by 9-aminoacridine in wild-type, uvrA and recA strains of Escherichia coli ; specificity within a hotspot (2007)
  • Author(s): Acharya N, Abu-Nasr NF, Kawaguchi G, Imai M, Yamamoto K.
  • Journal Title: J Radiat Res 48 Pages: 361-368
  • Peer Reviewed
• [Journal Article] Error-free RAD52 pathway and error-prone REV3 pathway determines spontaneous mutagenesis in Saccharomyces cerevisiae (2007)
  • Author(s): Endo K, Tago Y, Daigako Y, Yamamoto K
  • Journal Title: Genes Genet Syst 82(1) Pages: 35-42
  • NAID: 10024393693
  • Peer Reviewed
• [Journal Article] Role of the 5'3' exonuclease and Klenow fragment of Eschrichia coli DNA polymerase I in base mismatch repair (2007)
  • Author(s): Imai M, Tago Y, Ihara M, Kawata M, Yamamoto K
  • Journal Title: Mol Genet Genomics 278 Pages: 211-220
  • Peer Reviewed
• [Journal Article] Ames test-negative carcinogen, ortho-phenyl phenol, binds tubulin and causes aneuploidy in budding yeast (2007)
  • Author(s): Nunoshiba T, Watanabe E, Takahashi T, Daigaku Y, Ishikawa S, Mochizuki M, Ui A, Enomoto T, Yamamoto K.
  • Journal Title: Mutat Res 617(1-2) Pages: 90-97
  • Peer Reviewed
• [Journal Article] UvrA and UvrB enhance mutationsinduced by oxidized deoxyribonucleotides (2007)
  • Author(s): Hori M, Ishiguro C, Suzuki T, Nakagawa N, Nunoshiba T, Kuramitsu S, Yamamoto K.
  • Journal Title: DNA Repair (Amst) 6(12) Pages: 1786-1793
  • Peer Reviewed
• [Journal Article] UvrA and UvrB enhance mutations induced by oxidized deoxyribo-nucleotides. (2007)
  • Author(s): Mika Hori
  • Journal Title: DNA Repair (Amst) 6(12) Pages: 1786-1793
  • Peer Reviewed
• [Journal Article] Ames test-negative carcinogen, ortho-phenyl phenol, binds tubulin and causes aneuploidy in budding yeast. (2007)
  • Author(s): Tatsuo Nunoshiba
  • Journal Title: Mutat Res 617(1-2) Pages: 90-97
  • Peer Reviewed
• [Journal Article] Role of the 5'->3' exonuclease and Klenow fragment of Escherichia coli DNA polymerase I in base mismatch repair. (2007)
  • Author(s): Masaru Imai
  • Journal Title: Mol Genet Genomics 278(2) Pages: 211-20
  • Peer Reviewed
• [Journal Article] Frameshift mutations produced by 9-aminoacridine in wild-type, uvrA and recA strains of Escherichia coli; specificity within a hotspot (2007)
  • Author(s): Acharya N
  • Journal Title: J Radiat Res (Tokyo) 48(5): Pages: 361-368
  • Peer Reviewed
• [Journal Article] Error-free RAD52 pathway and error-prone REV3 pathway determines spontaneous mutagenesis in Saccharomyces cerevisiae. (2007)
  • Author(s): Endo K
  • Journal Title: Genes Genet Syst 82(1): Pages: 35-42
  • Peer Reviewed
• [Presentation] Centrosome amplification mediated by G2 delay leads to aneuploidy, as a result of misaligned chromosomes, by phenyl hydroquinone (2009)
  • Author(s): Masaru Imai, Ayumi Yamamoto, Tatsuo Nunoshiba, Jun-itiro Komura, Tetsuya Ono, Kazuo Yamamoto
  • Organizer: Gordon Research Conference(Mammalian DNA repair)
  • Place of Presentation: Ventura, CA
• [Presentation] Centrosome amplification mediated by G2 delay leads to aneuploidy, as a result of misaligned chromosomes, by phenyl hydroquinone (2009)
  • Author(s): Masaru Imai
  • Organizer: Gordon Research Conference (Mammalian DNA repair)
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Genotoxic and on-genotoxic effects of chemical substancesn that make an impact on genome instability, An International Symposium of Kyoto University RRI "Is There a Non-targeted Route in Radiationarcinogenesis Process? (2008)
  • Author(s): Ayumi Yamamoto, Youko Abe, Satoko Sawai, Masaru Imai, Kazuo Yamamoto
  • Organizer: Candidate PlayingCImportant Role
  • Place of Presentation: Osaka
  • Year and Date: 2008-12-18
• [Presentation] 出芽酵母に遺伝的不安定性を引き起こすもの一脱アミノ化ヌクレオチド損傷浄化機能Haml欠損と非変異原性発がん物質PHQ (2008)
  • Author(s): 布柴達男
  • Organizer: 日本環境変異原学会第36回大会シンポジウム『DNA修復と遺伝的不安定性』
  • Place of Presentation: 沖縄コンベンションセンター(宜野湾)
  • Year and Date: 2008-12-04
• [Presentation] 出芽酵母に遺伝的不安引き起こすもの脱アミノ化ヌクレオチド損傷浄化機能Ham1欠損と非変異原性発がん物質PHQ, シンポジウム「DNA修復と遺伝的不安定性」 (2008)
  • Author(s): 布柴達男
  • Organizer: 日本環境変異原学会第37回大会
  • Place of Presentation: 宜野湾
• [Presentation] G2/Mチェックポイントとゲノム安定性 (2008)
  • Author(s): 山本和生, 山本歩, 布柴達男
  • Organizer: 日本遺伝学会第80回大会,
  • Place of Presentation: 名古屋
• [Presentation] G2/M transition arrest functions in the formation of aneuploidy (2008)
  • Author(s): Kazuo Yamamoto, Ayumi Yamamoto, YRyo Matsuno, Masaru Imai
  • Organizer: The International Ataxia- Telangiectasia Workshop 2008
  • Place of Presentation: Ohtsu
• [Presentation] Phenyl hydroquinone induced stabilization of Swel by Hogl in budding yeast leads to arrest cell cycle at G2/M boundary (2007)
  • Author(s): Ayumi Yamamoto
  • Organizer: 1st Asia Conference on Environmental Mutagens日本環境変異原学会第36回大会
  • Place of Presentation: 北九州国際会議場(小倉)
  • Year and Date: 2007-11-29
• [Presentation] 非変異発がん物質PHQによるMAPKを介した染色体喪失;がん化への道 (2007)
  • Author(s): 今井 勝
  • Organizer: 日本放射線影響学会第50回大会 ワークショップ「放射線発がんの"非標的仮説"について
  • Place of Presentation: 幕張メッセ国際会議場(千葉)
  • Year and Date: 2007-11-15
• [Presentation] Ames試験陰性発がん物質の作用機構に見る発がん突然変異説の危うさ,シンポジウム「突然変異と染色体異数性は発がんの共謀者か?」 (2007)
  • Author(s): 山本和生, 今井勝, 松野亮, 山本歩, 布柴達男, 小野哲也
  • Organizer: 日本環境変異原学会公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-05-26
• [Presentation] Phenyl hydroquinone induced stabHog1 in budding yeast leads to arrest cell cycle atG2/M boundary (2007)
  • Author(s): Ayumi Yamamoto, Tatsuo Nunoshiba, Takemi Enomoto, Kazuo Yamamoto
  • Organizer: 1st Asia Conference onEnvironmental Mutagens / 36th Annual Meeting of the Japanese Environmental Mutagen Society
  • Place of Presentation: Kokura
• [Presentation] 非変異原性発がん物質PHQによるMAPKを介した染色体異数化~がんへの道~ ワークショップ 「放射線発がんの"非標的仮説"について」 (2007)
  • Author(s): 今井勝, 山本歩, 布柴達男, 小村潤一郎, 小野哲也, 山本和生
  • Organizer: 第50回放射線影響学会
  • Place of Presentation: 千葉
• [Remarks] 研究代表者は、内閣府食品安全委員会の農薬調査会専門委員を務めており、数々の農薬の一日摂取許容量ADI設定に関わっている。その際対象となる農薬の多くは本研究で取り上げている非変異・発がん物質であり、研究から得られた知見が貢献できる機会もある。
• [Remarks] このような取り組みを通じ、本研究成果の社会に向けての発信と次世代への科学・研究に対する興味の喚起に務めている。