Analysis of molecular targeting radiosensitization using DPYD depletion

2011 Fiscal Year Final Research Report

• Project/Area Number: 22791207
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Sapporo Medical University
• Principal Investigator: SOMEYA Masanori 札幌医科大学, 医学部, 講師 (60404711)
• Project Period (FY): 2010 – 2011
• Keywords: 放射線治療生物学 / 放射線増感剤 / 放射線

Research Abstract

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase(DPYD), partially inhibits homologous recombination(HR) repair and has a radiosensitizing effect. We investigated the mechanisms of sensitization of radiation by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA.

Research Products

• [Journal Article] Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation (2012)
  • Author(s): Masanori Someya, Masaru Takagi, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Masato HAREYAMA, Masakazu Fukushima
  • Journal Title: Jorunal of Radiation Research Volume: 53 Pages: 250-256
  • DOI: DOI:10.1269/jrr.11190DOI:10.1269/jrr.11190DOI:10.1269/jrr.11190
  • Peer Reviewed
• [Journal Article] The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization (2012)
  • Author(s): Masaru Takagi, Koh-ichi Sakata, Masanori Someya
  • Journal Title: Strahlentherapie and Onkologie Volume: 188 Pages: 255-261
  • DOI: DOI:10.1007/s00066-011-0043-6
  • Peer Reviewed
• [Journal Article] Gimeracil sensitizes cells to radiation via inhibition of homologous recombination (2011)
  • Author(s): Masaru Takagi, Koh-ichi Sakata, Masanori Someya
  • Journal Title: Radiotherapy and Oncology Volume: 96 Pages: 259-266
  • DOI: DOI:10.1016/j.radonc.2010.05.020
  • Peer Reviewed
• [Journal Article] Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination (2011)
  • Author(s): Koh-ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Minoru Toyota, Masaru Takagi, Masato Hareyama, Masakazu Fukushima
  • Journal Title: Cancer Science Volume: 102 Pages: 1712-6
  • DOI: DOI:10.1111/j.1349-7006.2011.02004.x
  • Peer Reviewed
• [Presentation] 放射線誘発NBS1, RPAフォーカスの共局在に対するギメラシルの影響 (2011)
  • Author(s): 染谷正則、坂田耕一、高木克、晴山雅人、田内広、松本義久、福島正和
  • Organizer: 第24回日本放射線腫瘍学会学術大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2011-11-17
• [Presentation] Radiosensitizing effects of Gimeracil (2010)
  • Author(s): Masanori Someya, Masaru Takagi, Koh擁chi Sakata, Hiroshi Tauchi, Yoshihisa Matsumoto, Masato Hareyama, Masakazu Fukushima
  • Organizer: 第56回Radiation Research Society
  • Place of Presentation: アメリカハワイ州
  • Year and Date: 2010-09-25