A picture of whole DNA modification induced by carcinogens: Whole-genome analysis for sequence specificity and vulnerability

• Project/Area Number: 25550036
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Meijo University
• Principal Investigator: OKAMOTO YOSHINORI 名城大学, 薬学部, 助教 (50512323)
• Co-Investigator(Kenkyū-buntansha): KOJIMA Nakao 鈴鹿医療科学大学, 医用工学部, 非常勤講師 (80333178)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: マウス胚性幹細胞 / 紫外線照射 / ゲノム修飾 / 未分化マーカー / 受精卵 / 脱メチル化 / LC/MS/MS / ＤＮＡ損傷 / 配列特異性 / 未分化因子 / シクロブタン型ピリミジンダイマー / DNA損傷

Outline of Final Research Achievements

The aim of this study is to take a whole picture of DNA damage induced by chemical carcinogens. I investigated benzo(a)pyrene which is containing in tobacco smoke and known as a potent carcinogen, and cyclobutane-pyrimidine dimer which is formed by UV exposure. In addition, this project achieved a great success in epigenetic analysis of mouse preimplantation zygote, in which methylcytidine was measured using a high-performance liquid chromatograph-triple quadrupole mass spectrometer.

Research Products

• [Int'l Joint Research] University of Bath(United Kingdom)
• [Journal Article] DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry (2016)
  • Author(s): Yoshinori Okamoto, Naoko Yoshida, Toru Suzuki, Nobuhiro Shimozawa, Maki Asami, Tomonari Matsuda, Nakao Kojima, Anthony C. F. Perry & Tatsuyuki Takada
  • Journal Title: Scientific Reports Volume: 該当しない Issue: 1 Pages: 19134-19134
  • DOI: 10.1038/srep19134
  • NAID: 120005822766
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oral administration of Brazilian propolis exerts estrogenic effect in ovariectomized rats (2015)
  • Author(s): Okamoto Y, Tobe T, Ueda K, Takada T, Kojima N
  • Journal Title: The Journal of Toxicological Sciences Volume: 40 Issue: 2 Pages: 235-242
  • DOI: 10.2131/jts.40.235
  • NAID: 130004904040
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed / Open Access
• [Journal Article] Thiol-mediated multiple mechanisms centered on selenodiglutathione determine selenium cytotoxicity against MCF-7 cancer cells. (2015)
  • Author(s): Tobe T., Ueda K., Ando M., Okamoto Y., Kojima N.
  • Journal Title: J. Biol. Inorg. Chem. Volume: NA Issue: 4 Pages: 687-694
  • DOI: 10.1007/s00775-015-1254-6
  • Peer Reviewed / Open Access
• [Journal Article] Neural Differentiation of Pluripotent Stem Cells and Application for Metal-induced Neural Toxicity Study (2014)
  • Author(s): Taniguchi Y., Tobe T., Hayami H., Okamoto Y., Ueda K., Takada T., Kojima N.
  • Journal Title: YAKUGAKU ZASSHI Volume: 134 Issue: 7 Pages: 793-795
  • DOI: 10.1248/yakushi.14-00017-3
  • NAID: 130004756445
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2014-07-01
  • Peer Reviewed / Open Access
• [Journal Article] Effects of organic and inorganic mercury(II) on gene expression via DNA conformational changes. (2014)
  • Author(s): Ueda K., Makino R., Tobe T., Okamoto Y., Kojima N.
  • Journal Title: Fund. Toxicol. Sci. Volume: 1 Pages: 73-79
  • NAID: 130005083332
  • Peer Reviewed / Open Access
• [Journal Article] A simple and convenient synthesis of a stable isotope-labeled 5-hydroxymehtyl-2’-deoxycytidine, the sixth base in mammalian DNA (2014)
  • Author(s): Takao Tobe，Yoshinori Okamoto，Tatsuyuki Takada，Nakao Kojima
  • Journal Title: J. Res. Inst. Meijo Univ. Volume: 13
  • Peer Reviewed
• [Journal Article] Roles of glutathione-mediated metabolites in the anti-tumor effects of selenium (2014)
  • Author(s): Takao Tobe, Koji Ueda, Yoshinori Okamoto, Motozumi Ando, Hiroyuki Nishida, Kazuo Ito, Nakao Kojima
  • Journal Title: J. Res. Inst. Meijo Univ. Volume: 13
  • NAID: 40020207659
  • Peer Reviewed
• [Journal Article] PRDM14 promotes active DNA demethylation through the Ten-eleven translocation (TET)-mediated base excision repair pathway in embryonic stem cells. (2014)
  • Author(s): Okashita, N., Kumaki, Y., Ebi, K., Nishi, M., Okamoto, Y., Nakayama, M., Hashimoto, S., Nakamura, T., Sugasawa, K., Kojima, N., Takada, T., Okano, M. and Seki, Y.
  • Journal Title: Development Volume: 141 Issue: 2 Pages: 269-280
  • DOI: 10.1242/dev.099622
  • Peer Reviewed
• [Presentation] DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry (2016)
  • Author(s): Yoshinori Okamoto, Naoko Yoshida, Toru Suzuki, Nobuhiro Shimozawa, Maki Asami, Tomonari Matsuda, Nakao Kojima, Anthony C. F. Perry, and Tatsuyuki Takada
  • Organizer: International Symposium on "Epigenome Dynamics and Regulation in Germ Cells 2016"
  • Place of Presentation: 京都
  • Year and Date: 2016-02-18
  • Int'l Joint Research
• [Presentation] マウス胚性幹細胞の発がん性多環芳香族炭化水素に対する感受性の比較 (2015)
  • Author(s): 長谷川祥子、戸邊隆夫、若原美沙紀、植田康次、岡本誉士典、高田達之、小嶋仲夫、神野透人
  • Organizer: 第61回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-07-04
• [Presentation] 紫外線曝露によるマウス胚性幹細胞のp53非依存的細胞死 (2014)
  • Author(s): 清水優希、戸邊隆夫、岡本誉士典、植田康次、高田達之、小嶋仲夫
  • Organizer: フォーラム2014：衛生薬学・環境トキシコロジー
  • Place of Presentation: つくば
  • Year and Date: 2014-09-19