The analysis of cell-type specific cellular responses under different irradiation conditions and dynamic regulation of p53 functions

• Project/Area Number: 23710069
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Hiroshima University
• Principal Investigator: KAWAI Hidehiko 広島大学, 原爆放射線医科学研究所, 助教 (30379846)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 応答 / p53 / 照射線量率 / iPS細胞 / 放射線影響 / ゲノム安定性維持機構 / 放射線 / 細胞応答 / ゲノム安定性

Research Abstract

Various types of human cultured cells, including induced pluripotent stem cells (hiPSCs), were cultured under chronic gamma-irradiation at low and middle dose-rates (10-1000 mGy/day). The cell-type specific cellular responses of these cells to irradiation and the underlying molecular mechanisms were analyzed to examine their dose-rate-dependence. A combination of chronic irradiation culture conditions and advanced high-throughput techniques, such as the next generation sequencing system and an automated image analyzing system, could reveal a variety of cellular systems for the maintenance of the genomic integrity and the molecular mechanisms of p53-dependent cellular responses.

Research Products

• [Journal Article] Aberrant microRNA expression in radiation-induced rat mammary cancer: the potential role of miR-194 overexpression in cancer cell proliferation (2013)
  • Author(s): Iizuka, D., Imaoka, T., Nishimura, M., Kawai, H., Suzuki, F., Shimada, Y.
  • Journal Title: Radiat Res. Volume: 179(2) Pages: 151-159
  • Peer Reviewed
• [Journal Article] Aberrant microRNA expression in radiation-induced rat mammary cancer: the potential role of miR-194 overexpression in cancer cell proliferation. (2013)
  • Author(s): Iizuka D, Imaoka T, Nishimura M, Kawai H, Suzuki F, Shimada Y.
  • Journal Title: Radiat Res Volume: 179(2) Pages: 151-9
  • Peer Reviewed
• [Journal Article] En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs (2012)
  • Author(s): Masuda, Y., Suzuki, M., Kawai, H., Hishiki, A., Hashimoto, H., Masutani, C., Hishida, T., Suzuki, F., Kamiya, K
  • Journal Title: Nucleic Acids Res Volume: 40(20) Pages: 10394-10407
  • Peer Reviewed
• [Journal Article] Aurora kinase-A inactivates DNA damage-induced apoptosis and spindle assembly checkpoint response functions of p73 (2012)
  • Author(s): Katayama, H., Wang, J., Treekitkarnmongkol, W., Kawai, H., Sasai, K., Zhang, H., Wang, H., Adams, HP., Jiang, S., Chakraborty, SN., Suzuki, F., Arlinghaus, RB., Liu, J., Mobley, JA., Grizzle, WE., Wang, H., Sen, S.
  • Journal Title: Cancer Cell Volume: 21(2) Pages: 196-211
  • Peer Reviewed
• [Journal Article] Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex (2012)
  • Author(s): Masuda, Y., Suzuki, M., Kawai, H., Suzuki, F., Kamiya, K.
  • Journal Title: Nucleic Acids Res. Volume: 40(3) Pages: 1065-1076
  • NAID: 120005147856
  • Peer Reviewed
• [Journal Article] En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs. (2012)
  • Author(s): Masuda Y, Suzuki M, Kawai H, Hishiki A, Hashimoto H, Masutani C, Hishida T, Suzuki F, Kamiya K.
  • Journal Title: Nucleic Acids Res Volume: 40(20) Pages: 10394-407
  • Peer Reviewed
• [Journal Article] Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex. (2012)
  • Author(s): Masuda, Y., Suzuki, M., Kawai, H., Suzuki, F., and Kamiya, K.
  • Journal Title: Nucleic Acids Res. Volume: 40(3) Pages: 1065-1076
  • NAID: 120005147856
  • Peer Reviewed
• [Journal Article] Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73. (2012)
  • Author(s): Katayama, H., Wang, J., Treekitkarnmongkol, W., Kawai, H., et al.
  • Journal Title: Cancer Cell. Volume: 21(2) Pages: 196-211
  • Peer Reviewed
• [Journal Article] The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo (2011)
  • Author(s): Huang, L., Yan, Z., Liao, X., Li, Y., Yang, J., Wang, ZG., Zuo, Y., Kawai, H., Shadfan, M., Ganapathy, S., Yuan, ZM
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 108(29) Pages: 12001-12006
  • Peer Reviewed
• [Journal Article] The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo. (2011)
  • Author(s): Huang, L., Yan, Z., Liao, X., Li, Y., Yang, J., Wang, ZG., Zuo, Y., Kawai, H., Shadfan, M., Ganapathy, S., and Yuan, ZM.
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 108(29) Pages: 12001-12006
  • Peer Reviewed
• [Presentation] Comprehensive analysis of cellular responses to chronic γ-irradiation (2013)
  • Author(s): 河合秀彦
  • Organizer: 3rd International Symposium of RIRBM
  • Place of Presentation: 広島市
  • Year and Date: 2013-02-13
• [Presentation] The role of p53 in human iPS cells in the cellular response to DNA-damage (2012)
  • Author(s): 河合秀彦
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-12-13
• [Presentation] 異なる線量率のγ線照射下での 細胞応答の多次元解析 (2012)
  • Author(s): 河合秀彦
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台市
  • Year and Date: 2012-09-08
• [Presentation] 慢性的な放射線照射に対する細胞応答機構の解析 (2012)
  • Author(s): 河合秀彦
  • Organizer: 第37回中国地区放射線影響研究会
  • Place of Presentation: 広島市
  • Year and Date: 2012-07-27
• [Presentation] γ線の照射環境下での細胞応答の線量率依存性の解析 (2011)
  • Author(s): 河合秀彦
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-11-19
• [Presentation] 恒常的な放射線照射に対する細胞応答の線量率依存性の解析 (2011)
  • Author(s): 河合秀彦
  • Organizer: 第52回原子爆弾後障害研究会
  • Place of Presentation: 広島市
  • Year and Date: 2011-06-05
• [Presentation] 恒常的な放射線照射に対する細胞応答の線量率依存性の解析 (2011)
  • Author(s): 河合秀彦
  • Organizer: 第52回原子爆弾後障害研究会
  • Place of Presentation: 広島
• [Presentation] γ線の照射環境下での細胞応答の線量率依存性の解析 (2011)
  • Author(s): 河合秀彦
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸
• [Presentation] 慢性的な放射線照射に対する細胞応答機構の解析
  • Author(s): 河合秀彦
  • Organizer: 第３７回中国地区放射線影響研究会
  • Place of Presentation: 広島市
• [Presentation] The role of p53 in human iPS cells in the cellular response to DNA-damage
  • Author(s): 河合秀彦
  • Organizer: 第３５回日本分子生物学会年回
  • Place of Presentation: 福岡市