Screening of the candidate gene involved in clinically relevant radioresistance

• Project/Area Number: 19710049
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tohoku University
• Principal Investigator: KUWAHARA Yoshikazu Tohoku University, 加齢医学研究所, 助教 (00392225)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,630,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: 放射線耐性 / 放射線療法 / 遺伝子発現 / コロニー形成法 / 肝癌 / 放射線

Research Abstract

放射線療法時に見られる放射線耐性細胞は予後を左右する重要な因子の1つである。本研究では、2Gy/dayのX線を30日以上照射し続けても増殖する放射線耐性細胞株の樹立を試み、解析した。その結果、放射線耐性細胞では効率的にX線で誘発されるDNA2本鎖切断を修復している事が分かった。また、PCR based differential display法による遺伝子発現解析から、放射線耐性細胞に特異的に発現が変動している遺伝子が幾つか得られた。

Research Products

• [Journal Article] Long incubation period for the induction of cancer by thorotrast is attributed to the uneven irradiation of liver cells at the microscopic level. (2009)
  • Author(s): Yamamoto Y, Usuda N, Takatsuji T, Kuwahara Y, Fukumoto M
  • Journal Title: Radiat Res 171 Pages: 494-503
  • Peer Reviewed
• [Journal Article] Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays (2009)
  • Author(s): Kuwahara Y, Li L, Baba T, Nakagawa H, Shimura T, Yamamoto Y, Ohkubo Y, Fukumoto M
  • Journal Title: Cancer Sci 100 Pages: 747-752
  • NAID: 10025144817
  • Peer Reviewed
• [Journal Article] Stabilities of 67Ga- and 111In-labeled transferrin in vitro (2009)
  • Author(s): Ohtake Y, Maruko A, Kuwahara Y, Fukumoto M, Ohkubo Y
  • Journal Title: Protein Pept Lett 16 Pages: 138-142
  • Peer Reviewed
• [Journal Article] Long incubation period from the induction of cancer by Thorotrast is at tributed to the uneven irradiation of liver cells at the microscopic level (2009)
  • Author(s): Yamamoto Y., Usuda N., Takatsuji T., Kuwahara Y., Fukumoto M.
  • Journal Title: Radiation Research 171 Pages: 494-503
  • Peer Reviewed
• [Journal Article] Clinically relevant radioresistant cells efficiently repair DNA double-stra nd breaks induced by X-rays (2009)
  • Author(s): Kuwahara Y., Li L., Baba T., Nakagawa H, Shimura T, Yamamoto Y, Ohkubo Y, Fukumoto M.
  • Journal Title: Cancer Science 100 Pages: 747-752
  • NAID: 10025144817
  • Peer Reviewed
• [Journal Article] Stabilities of 67Ga- and 111In-labeled transferrin in vitro (2009)
  • Author(s): Ohtake Y, Maruko A., Kuwahar a K., Fukumoto M., Ohkubo Y.
  • Journal Title: Protein Peptid Letter 16 Pages: 138-142
  • Peer Reviewed
• [Journal Article] Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight (2008)
  • Author(s): Baba T, Nishimura M, Kuwahara Y, Ueda N, Naitoh S, Kume M, Yamamoto Y, Fujita J, Funae Y, Fukumoto M
  • Journal Title: Pathol Int 58 Pages: 589-595
  • NAID: 10027377866
  • Peer Reviewed
• [Journal Article] Neutrophil gelatinase-associated lipocalin acts as a protective factor against H2O2 toxicity (2008)
  • Author(s): Roudkenar MH, Halabian R, Ghasemipour Z, Roushandeh AM, Rouhbakhsh M, Nekogoftar M, Kuwahara Y, Fukumoto M, Shokrgozar MA
  • Journal Title: Arch Med Res 396 Pages: 560-566
  • Peer Reviewed
• [Journal Article] Gene expression profiles in mouse liver cells after exposure to different types of radiation (2008)
  • Author(s): Roudkenar MH, Li L, Baba T, Kuwahara Y, Nakagawa H, Wang L, Kasaoka S, Ohkubo Y, Ono K, Fukumoto M
  • Journal Title: J Radiat Res 49 Pages: 29-40
  • NAID: 110006570525
  • Peer Reviewed
• [Journal Article] Induction of apoptosis on K562 cell line and double strand breaks on colon cancer cell line expressing high affinity receptor for granulocyte macrophage-colony stimulating factor (GM-CSF). (2008)
  • Author(s): Roudkenar MH, Bouzari S, Kuwahara Y, Roushandeh AM, Baba T, Oloomi M, Fukumoto M
  • Journal Title: Iran Biomed J 12 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight (2008)
  • Author(s): Baba T, Nishimura M, Kuwahar a Y, Ueda N, Naitoh S, Kume M, Yamamoto Y, Fujita J, Funa e Y, Fukumoto M.
  • Journal Title: Pathology International 58 Pages: 589-595
  • Peer Reviewed
• [Journal Article] Gene expression profiles in mouse liver cells after exposure to different types of radiation. (2008)
  • Author(s): Roudkenar MH.
  • Journal Title: J Radiat Res. 49 Pages: 29-40
  • Peer Reviewed
• [Journal Article] Induction of apoptosis on K562 cell line and Double strand breaks on colon cancer cell line expressing high affinity receptor for Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). (2008)
  • Author(s): Roudkenar MH.
  • Journal Title: Iranian Biomedical J. 12 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation (2007)
  • Author(s): Wang L, Kuwahara Y, Li L, Baba T, Shin RW, Ohkubo Y, Ono K, Fukumoto M
  • Journal Title: Int J Radiat Biol 83 Pages: 433-442
  • Peer Reviewed
• [Journal Article] Oxidative stress induced Lipocalin 2 gene expression : addressing its expression under the harmful conditions (2007)
  • Author(s): Roudkenar MH, Kuwahara Y, Baba T, Roushandeh AM, Ebshima S, Abe S, Ohkubo Y, Fukumoto M
  • Journal Title: J Radiat Res 48 Pages: 39-44
  • NAID: 110006570515
  • Peer Reviewed
• [Journal Article] Assessment of GM-CSF receptors by real-time RT-PCR on cell lines expressing high and low affinity receptors and their relation to cytotoxic effect of chimeric protein (StxA1-GM-CSF) (2007)
  • Author(s): Roudkenar MH, Bouzari S, Oolomi M, Kuwahara Y, Roushandeh AM, Baba T, Fukumoto M
  • Journal Title: DARU 15 Pages: 151-155
  • Peer Reviewed
• [Journal Article] Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation. (2007)
  • Author(s): Wang L.
  • Journal Title: Int J Radiat Biol. 83 Pages: 433-442
  • Peer Reviewed
• [Journal Article] Assessment of GM-CSF receptors by real-time RT-PCR on cell lines expressing high and low affinity receptors and their relation to cytotoxic effect of chimeric protein (StxA1-GM-CSF). (2007)
  • Author(s): Roudkenar MH.
  • Journal Title: DARU 15 Pages: 151-155
  • Peer Reviewed
• [Presentation] ラパマイシン投与による放射線耐性細胞のX線に対する増感効果 (2008)
  • Author(s): 桑原 義和, 森 美由紀, 中川 浩伸, 志村 勉, 福本 学
  • Organizer: 第51回日本放射線影響学会大会
  • Place of Presentation: 福岡
• [Presentation] 放射線感受性を高感度に検出するHigh density survival assayの改良開発 (2008)
  • Author(s): 桑原 義和, 中川 浩伸, 森 美由紀, 志村 勉, 福本 学
  • Organizer: 第51回日本放射線影響学会大会
  • Place of Presentation: 福岡
• [Presentation] アラジャム ミリット 複製フォーク進行阻害により誘導されるDNA2重鎖切断の生成機構とその修復 (2008)
  • Author(s): 志村 勉, 桑原 義和, 福本 学
  • Organizer: 第51回日本放射線影響学会大会
  • Place of Presentation: 福岡
• [Presentation] DNA損傷応答遺伝子ric1の機能解析 (2008)
  • Author(s): 日高 征幸, 尾田 正二, 漆原 佑介, 桑原 義和, 福本 学, 三谷 啓志
  • Organizer: 第51回日本放射線影響学会大会
  • Place of Presentation: 福岡
• [Presentation] X線長期被ばくの生物影響:サイクリンD1の過剰発現によるG1/Sチェックポイント機構の損失 (2008)
  • Author(s): 志村 勉, 角田 智, 中川 浩伸, 桑原 義和, 福本 学
  • Organizer: 第51回日本放射線影響学大会
  • Place of Presentation: 福岡
• [Presentation] Rapamycin abrogates the phenotype of acquired radioresistance in vivo (2008)
  • Author(s): Kuwahara Y, Nakagawa H, Shimura T, Mori M, Kurihara A, Baba T, Fukumoto M
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Analysis of chromosomal loci with high frequency of loss of heterozygosity in Thorotrast-induced liver tumors (2008)
  • Author(s): Baba T, Nakagawa H, Kuwahara Y, Kurihara A, Fukumoto M.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Dose chronic exposure to ionizing radiation induce somatic mutations in the D-loop of mitochondrial DNA? (2008)
  • Author(s): Kurihara A, Kuwahara Y, Shimura T, Yamamoto Y, Fukumoto M
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Long incubation period of cancer by internal irradiation is attributed to the uneven irradiation at microscopic level (2008)
  • Author(s): Yamamoto Y, Kuwahara Y, Fukumoto M
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Establishment and characterization of a radioresistant cell line from oral squamous cell carcinoma cell line, SAS cells (2008)
  • Author(s): Nakagawa H, Kuwahara Y, Miyashita H, Mori S, Shimura T, Mori M, Baba T, Fukumoto M
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] ヒト放射線内部被ばくによる肝発がんの分子機構 : トロトラスト症から (2008)
  • Author(s): 福本 学、桑原 義和
  • Organizer: 第40回日本臨床分子形態学会総会 (シンポジウム)
  • Place of Presentation: 福岡
• [Presentation] 肝腫瘍における染色体13q31のLOH解析 (2007)
  • Author(s): 馬場 泰輔、桑原 義和、井上 和也、栗原 愛、福本 学
  • Organizer: 第4回東北大学バイオサイエンスシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-06-04
• [Presentation] 放射線耐性細胞株の樹立とその特徴解析 (2007)
  • Author(s): 桑原 義和、馬場 泰輔、井上 和也、栗原 愛、進藤 智彦、福本 学
  • Organizer: 第4回東北大学バイオサイエンスシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-06-04
• [Presentation] 肝腫瘍における染色体13q31のLOH解析 (2007)
  • Author(s): 馬場 泰輔
  • Organizer: 第4回 東北大学バイオサイエンスシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-06-04
• [Presentation] 放射線耐性細胞株の樹立とその特徴解析 (2007)
  • Author(s): 桑原 義和
  • Organizer: 第4回 東北大学バイオサイエンスシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-06-04
• [Presentation] 放射線耐性細胞ではX線で誘発されるDNAの2本鎖切断は正確に修復される (2007)
  • Author(s): 桑原 義和、馬場 泰輔、井上 和也、栗原 愛、福本 学
  • Organizer: 第50回日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] ミトコンドリアのD-loop領域に放射線被ばくに特異的な変異は存在するか? (2007)
  • Author(s): 栗原 愛、王 ル、井上 和也、桑原 義和、山本 雄造、福本 学
  • Organizer: 第50回日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] 放射線耐性及び長期放射線被ばく細胞におけるゲノムワイドなメチル化領域の探索 (2007)
  • Author(s): 井上 和也、高橋 由明、村田 和弘、桑原 義和、志村 勉、福本 学
  • Organizer: 第50回日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] 分離培養したラット肝構成細胞のγ線に対する遺伝子発現変化 (2007)
  • Author(s): 馬場 泰輔、桑原 義和、井上 和也、栗原 愛、鈴木 実、小野 公二、福本 学
  • Organizer: 第50回日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] Histopathological study of rat brain exposed to X-ray microplanar beams (2007)
  • Author(s): Kurihara A, Kondoh T, Kashino G, Ono K, Shinohara K, Kuwahara Y, Fukumoto M
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Loss of heterozygosity on chromosome 8q21.2-q21.3 which is associated with Thorotrast-induced liver tumors (2007)
  • Author(s): Baba T, Kuwahara Y, Kurihara A, Fukumoto M
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Characterization of radioresistant cells established by long-term X-ray exposure (2007)
  • Author(s): Kuwahara Y, Baba T, Kurihara A, Fukumoto M
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] The mutation of ric1 induces delayed repair of DNA double strand breaks, cell death inhibition and early checkpoint release (2007)
  • Author(s): Hidaka M, Oda S, Kuwahara Y, Fukumoto M, Mitani H
  • Organizer: 13th International congress of radiation research
  • Place of Presentation: San Francisco, USA
• [Presentation] Methylation of SOCS3 and p15 in carbon-ioninduced thymic lymphomas of B6C3F1 mice (2007)
  • Author(s): Shimada Y, Ebishima S, Yamaguchi Y, Kuwahara Y, Kakinuma S, Amasaki Y, Nishimura M, Imaoka T, Kobayashi Y, Sato Y
  • Organizer: 13th International congress of radiation research
  • Place of Presentation: San Francisco, USA
• [Presentation] Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation (2007)
  • Author(s): Kurihara A, Wang L, Kuwahara Y, Baba T, Ono K, Fukumoto M
  • Organizer: 13th International congress of radiation research
  • Place of Presentation: San Francisco, USA
• [Presentation] Histopathological study of rat brain exposed to x-ray microplanar Beams. (2007)
  • Author(s): Kurihara A.
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Loss of heterozygosity on chromosome 8q21.2-q21.3 which is associated with Thorotrast-induced liver tumors. (2007)
  • Author(s): Baba T.
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Characterization of radioresistant cells established by long-term X-ray exposure. (2007)
  • Author(s): Kuwahara Y.
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 放射線耐性細胞ではX線で誘発されるDNAの2本鎖切断は正確に修復される (2007)
  • Author(s): 桑原 義和
  • Organizer: 第50回 日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] ミトコンドリアのD-loop領域に放射線被ばくに特異的な変異は存在するか? (2007)
  • Author(s): 栗原愛
  • Organizer: 第50回 日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] 放射線耐性及び長期放射線被ばく細胞におけるゲノムワイドなメチル化領域の探索 (2007)
  • Author(s): 井上和也
  • Organizer: 第50回 日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] 分離培養したラット肝構成細胞のγ線に対する遺伝子発現変化 (2007)
  • Author(s): 馬場 泰輔
  • Organizer: 第50回 日本放射線影響学会大会
  • Place of Presentation: 千葉
• [Presentation] The mutation of ricl induces delayed repair of DNA double strand breaks, cell death inhibition and early checkpoint release. (2007)
  • Author(s): Hidaka M.
  • Organizer: 13th International congress of radiation research
  • Place of Presentation: California, USA
• [Presentation] Methylation of SOCS3 and p15 in carbon-ioninduced thymic lymphomas of B6C3F1 mice (2007)
  • Author(s): Shimada Y.
  • Organizer: 13th International congress of radiation research
  • Place of Presentation: California, USA
• [Presentation] Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation. (2007)
  • Author(s): Kurihara A.
  • Organizer: 13th International congress of radiation research
  • Place of Presentation: California, USA
• [Remarks]
  • URL: http://www.idac.tohoku.ac.jp/dep/path/
• [Remarks] 新聞掲載
• [Remarks] Medical Tribune VOL. 41 NO. 3 p.35 2008