Analysis of lethal DNA damage induced by ionizing radiation and aldehydes

• Project/Area Number: 26340023
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Hiroshima University
• Principal Investigator: NAKANO TOSHIAKI 広島大学, 理学研究科, 助教 (10526122)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 損傷 / DNA修復 / 生物影響 / 修復 / ^

Outline of Final Research Achievements

DNA double strand breaks (DSBs) are the most critical DNA lesions for cell death. However, other lethal lesions such as DNA-protein cross-links (DPCs) and DNA interstrand cross-links (ICLs) are produced by DNA damaging agents. Here we estimated the roles of DPCs and ICLs in the lethal events of cells upon exposure to aldehydes and X-rays. DNA repair was essential for alleviating the cytotoxic effect of weakly toxic aldehydes such as saturated aldehydes. Our data also suggest that ICLs are the critical cytotoxic DNA damage induced by aldehydes. X-rays produced more DPCs in hypoxic tumors than in normoxic tumors. X-rays generated two types of DPC that differed according to their rate of removal from the genome. The half-lives of the rapidly removed components of DPCs and DSBs were similar, but those of the slowly removed components of DPCs were markedly different. The long half-life and abundance of the slowly removed DPCs may exert deleterious effects on cells in conjunction with DSBs.

Research Products

• [Journal Article] Restriction glycosylases: involvement of endonuclease activities in the restriction process. (2017)
  • Author(s): Ming-Zhang Xie, Tomoyuki Matsuzaka, Hirokazu Yano, Yoshikazu Furuta, Toshiaki Nakano, Ken Ishikawa, Masaki Fukuyo, Noriko Takahashi, Yutaka Suzuki, Sumio Sugano, Hiroshi Ide and Ichizo Kobayashi
  • Journal Title: Nucleic Acids Res Volume: 45 Pages: 1392-1403
  • DOI: 10.1093/nar/gkw1250
  • Peer Reviewed / Open Access
• [Journal Article] Radiation-induced DNA-protein cross-links:Mechanisms and biological significants (2017)
  • Author(s): Toshiaki Nakano, Xu Xu, Salem Amir M.H., and Hirohsi Ide
  • Journal Title: Free Radic Biol Med Volume: 16 Pages: 31075-31079
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Aldehydes with high and low toxicities inactivate cells by damaging distinct cellular targets (2016)
  • Author(s): Ming-Zhang Xie, Mahmoud I. Shoulkamy, Amir M.H. Salem, Shunya Oba, Mizuki Godaa, Toshiaki Nakano and Hiroshi Ide
  • Journal Title: Mutation Research Volume: 786 Pages: 41-51
  • DOI: 10.1016/j.mrfmmm.2016.02.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Induction of DNA-protein cross-links by ionizing radiation and their elimination from the genome (2015)
  • Author(s): Nakano T., Mitsusada Y., Salem A., Shoulkamy M., Sugimoto T., Hirayama R., Uzawa A., Furusawa Y., and Ide H.
  • Journal Title: Mutation Research Volume: 771 Pages: 45-50
  • DOI: 10.1016/j.mrfmmm.2014.12.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Restriction-modification system with methyl-inhibited base excision and abasic-site cleavage activities (2015)
  • Author(s): Masaki Fukuyo, Toshiaki Nakano, Yingbiao Zhang, Yoshikazu Furuta, Ken Ishikawa, Miki Watanabe-Matsui, Hirokazu Yano, Takeshi Hamakawa, Hiroshi Ide, Ichizo Kobayashi
  • Journal Title: Nucleic Acids Research Volume: Vol. 43, No. 5 Issue: 5 Pages: 2841-2852
  • DOI: 10.1093/nar/gkv116
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 酸化剤が誘発するDNA-タンパク質クロスリンク損傷の検出 (2016)
  • Author(s): 瀬畑 敬文，久保山 政弥，徐 徐，Salem Amir，Shoulkamy Mahmoud，井出 博，中野 敏彰
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] 放射線が誘発するDNA-タンパク質クロスリンク損傷の解析 (2016)
  • Author(s): 瀬畑敬文，久保山政弥，徐 徐, Salem Amir, Shoulkamy Mahmoud, 平山亮一, 鵜澤玲子, 中野敏彰, 井出博
  • Organizer: 第59回日本放射線影響学会
  • Place of Presentation: 広島
  • Year and Date: 2016-10-26
• [Presentation] ANALYSIS OF DNA-PROTEIN CROSS-LINKS INDUCED BY ALDEHYDES (2016)
  • Author(s): Toshiaki Nakano, Mizuki Goda, Ming-Zang Xie, Amir Salem, Mahmoud Shoulkamy, Hiroshi Ide
  • Organizer: 14th international workshop on radiation damage to DNA
  • Place of Presentation: Melborune (Austlaria)
  • Year and Date: 2016-03-21
  • Int'l Joint Research
• [Presentation] X線照射したマウス腫瘍におけるDNA-タンパク質クロスリンクの生成・除去動態 (2015)
  • Author(s): 中野敏彰、謝明章、合田美月、Mahmoud Ibrahim Shoulkamy、Amir Salem、井出博
  • Organizer: 日本放射線影響学会 第40回大会
  • Place of Presentation: 福岡市 九州大学馬出キャンパス
  • Year and Date: 2015-11-27
• [Presentation] DNA損傷依存的および非依存的なアルデヒドの細胞毒性発現機構 (2015)
  • Author(s): 中野敏彰、謝明章、合田美月、Mahmoud Ibrahim Shoulkamy、Amir Salem、井出博
  • Organizer: 日本環境変異原学会 第44回大会
  • Place of Presentation: 富山県 富山市
  • Year and Date: 2015-10-16
• [Presentation] アルデヒドが誘発するDNA損傷の解析 (2014)
  • Author(s): 中野 敏彰, 謝 明章, 合田 美月, Mahmoud I. Shoulkamy, 井出 博
  • Organizer: 第43回 日本環境変異原学会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-04 – 2014-12-05
• [Presentation] アルデヒドが誘発するゲノム損傷の解析 (2014)
  • Author(s): 中野 敏彰, 謝 明章, Mahmoud I. Shoulkamy, Amir M.H. Salem, 井出 博
  • Organizer: 第37回 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Effect of DNA-protein cross-links on the translocation of replicative DNA helicases (2014)
  • Author(s): Toshiaki Nakano, Mahmoud I. Shoulkamy, Amir M.H. Salem, Ming-Zang Xie, Hiroshi Ide
  • Organizer: 13th International Workshop on Radiation Damage to DNA
  • Place of Presentation: Cambridge, MA, USA
  • Year and Date: 2014-06-14 – 2014-06-18