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Predictive assays of normal tissue damage using molecular, cellular and tissue methods

Research Project

Project/Area Number 08457247
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

ANDO Koichi  Natl Inst Radiol Sci, 3rd Research Group, head, 第3研究グループ, 研究員 (00159526)

Co-Investigator(Kenkyū-buntansha) MARCO DURANT  放射線医学総合研究所, 第3研究グループ, STAフェロー
MAEZAWA Hiroshi  TOKAI University School of Medicine Dep.Radiology, Assistant Professor, 放射線科学, 講師 (00138653)
SUZUKI Masao  Natl Inst Radiol Sci, 3rd Research Group, Senior Researcher, 第3研究グループ, 研究員 (70281673)
AKASHI Makoto  Natl Inst Radiol Sci, Div.Radiation Health, head, 放射線障害医療部, 研究員 (10222514)
DURANTE Marco  Natl Inst Radiol Sci, 3rd Research Group, head Visiting Scientist
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordscarbon ions / fractionation / skin / cultured epithelial cells / chromatin / TNF / NFkB / HGF / アポトーシス / Bax / Bcl-2
Research Abstract

We have investigated relationship between cell lethality and chromatin damage induced by ionizing radiation. Cultured normal cells derived from human skin were irradiated with X rays or carbon ions. Premature condensed chromosome (PCC) method indicated that residual chromatin damages increased with dose for X rays as well as carbon ions. RBE of carbon ions was similar between colony formation and the residual PCC.Cacyculin could efficiently induced PCC in human lymphocytes, suggesting the chemical would be valuable for clinical use in future. Radiosensitivity of immortalized human epithelial cells was stable during fractionated irradiations with carbon ions for 5 fractions with an interval time of 4 hours. Isoeffect doses for carbon ions depended on LET and the number of fractions in mouse skin reaction. Fe plot analysis suggested that either cellular repair or repopulation would be changed during fractionated irradiation. Irradiation with X rays to human monocytic leukemia HTP-1 induced TNF production, and also activated NFkB in nuclear protein. These results suggest that radiation-induced cell lethality stems from chromatin damages in critical cells whereas radiation-induced gene expression including also take place for repopulation and tissue repair. Further analyze of gene expression and chromatin damages is required for developing new predictive assays.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] H.Maezawa, Y.Furusawa, K.Kobayashi, K.Hieda, M.Suzuki, N.Usami, A.Yokota, T.Mori: "Lethal effect of K-shell absorption of intracellular phosphorus on wild-type and radiation sensitive mutants of Escherichia coli" Acta Oncologica. 35(7). 889-894 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Namba, T.Irie, K.Fukushi, M.Iyo, T.Hashimoto and K.Ando: "Time courses of changes in cerebral blood flow and bloodbrain barrier integrity by focal proton radiation in the rat," Neurological Research. 18. 83-86 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Furusawa, H.Maezawa, K.Takakura, K.Kobayashi, K.Hieda: "Radiolytic products of bromodeoxyuridine in solids by C060 gamma-rays and monoenergetic soft-X-rays at the Kabsorption edge of bromine" Acta Oncologica. 35(7). 877-882 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hieda, T.Hirono, A.Azami, M.Suzuki, Y.Furusawa, H.Maezawa N.Usami, A.Yokota, K.Kobayashi,: "Single-and double-strand breaks in pBR322 plasmid DNA by monochromatic X-rays on and off the K-absorption peak of phosphorus" Int.J.Radiation Biol.70(4). 437-445 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, M.Watanabe, T.Kanai, Y.Kase, F.Yatagai, K.Kato and S.Matsubara: "LET dependence of cell death,mutation induction and chromatin damage in human cells irradiated with sccelerated carbon ions" Advances in Space Research. 18. (1/2)127-(1/2)136 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 鈴木 雅雄、加瀬 陽子、金井 達明、安藤 興一、渡辺 正己、谷田貝 文夫: "重粒子線で誘発されるクロマチン切断誘発のLET依存性" 宇宙生物科学. 10. 224-225 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Uehara, M.Miyoshi, K.Andou, S.Koike, K.Masuda: "Early skin shrinkage,late skin contraction and leg contracture of mice exposed to two equal fractions of neutron" J.Jpn.Soc.Ther.Radiol.Oncol.8. 21-27 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Nomura, Y.Nakata, T.Inoue, A.Uzawa, S.Itamura, K.Nerome, M.Akashi and G.Suzuki: "In vivo induction of cytotoxic Tlymphocutes specific for a single epitope introduced into an unrelated molecule" J.Immunol.Methods. 193. 41-49 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Akashi, S.Takagi and M.Hachiya: "Anti-cancer agent OK432 induces manganese superoxide dismutasc in human granulocytcs." Int.J.Cancer. 68. 384-390 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Shinohara, M.Akashi, A.F.Combart, R.Yang and H.P.Koeffler: "Tumor necrosis factor a:Posttranscriptional stabilization of WAF1 mRNA in p53-deficient human leukemic cells" J.Cellular Physiology. 166. 568-576 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, Y.Kase, T.Kanai, F.Yatagai and M.Watanabe: "LET dependence of cell death and chromatin-break induction in normal human cells irradiated by neon-ion beams." International Journal of Radiation Biology. 72. 497-503 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kumiko Fukutsu, Tatsuaki Kanai, Yoshiya Furusawa and Koichi Ando: "Response of Mouse Intestine after Single and Fractionated Irradiation of Accelerated Carbon Ions with a Spread-Out Bragg Peak." Radiation Research. 148. 168-174 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Maezawa, M.Suzuki, A.Yokoya, N.Usami, K.Kobayashi: "Repair of chromation breaks produced by monochromatic X-rays with energies of around K-shell absorption edge of phosphorus in V79 cells" Photon Factory Activity Rep.14. 420 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 鈴木 雅雄: "クロマチン損傷と放射線感受性の相関性" Japanese Journal of Cancer Clinics. 43. 156-162 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 鈴木 雅雄、加瀬 陽子、金井 達明、安藤 興一: "HIMAC炭素イオンビーム照射によるヒト正常細胞の細胞死におけるLET依存性" 宇宙生物科学. 11. 270-271 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Hachiya, S Shimizu, Y Osawa, M Akashi.: "Endogenous production of tumor necrosis factor is required for manganese superoxide dismutase expression in the human monocytic cell line THP-1." Biochem J. 328. 615-623 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Iizuka, K.Ando, T.Aruga, H.Itsukaichi, K.Fukutsu, H.Nagasawa and H.Moriya: "Effects of reoxygenation on repair of potentially lethal radiation damage in cultured MG-63 osteosarcoma cells" Radiation Research. 147. 179-184 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Murakami, H.Tsujii, Y.Furusawa, K.Ando, T.Kanai, S.Yamada, K.Kawachi: "Medical and other applications of high-energy heavy-ion beams from HIMAC" Journal of Nuclear Materials. 248. 360-368 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 安藤 興一: "重粒子線の生物学" エネルギーレビュー. 17(10). 14-16 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, Y.Watanabe, Y.Kase, T.Kanai and F.Yatagai: "LET dependence of cell death,mutation induction and chromosome damage irradiated by accelerated carbon ions.Solar-Terrestrial Predictions-V" Proceedings of a Workshop at Hitachi. 486-494 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, Y.Kase, T.Kanai and K.Ando: "Correlation between cell death and non-rejoining PCC breaks by carbon-ion beams" Advances in Space Research. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M Akashi, HP Koeffler.: "Li-Fraumeni syndrome and the role of the p53 tumors uppressor gene in cancer susceptibility." Clin.Obst.Gynecol.41. 172-199 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ando, S.Koike, K.Nojima, Y-J.Chen, C.Ohira, S.Ando, N.Kobayashi, T.Ohbuchi, W.Shimizu and T.Kanai: "Mouse skin reactions following fractionated irradiation with carbon ions." Int.J.Radiation Biology. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Maezawa, Y.Furusawa, K.Kobayashi, K.Hieda, M.Iyo, T.Suzuki, N.Usami, A.Yokota, T.Mori: "Lethal effect of K-shell absorption of intracellular phosphorus on wild-type and radiation sensitive mutants of Escherichia coil." Acta Oncologica. 35(7). 889-894 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Namba, T.Irie, K.Fukushi, M.Hashimoto and K.Ando: "Time courses of changes in cerebral blood flow and blood-brain barrier integrity by focal proton radiation in the rat" Neurological Research. 18. 83-86 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Furusawa, H.Maezawa, K.Takakura, K.Kobayashi, K.Hieda: "Radiolytic products of bromodeoxyuridine in solids by C0-60 gamma-rays and monoenergetic soft-X-rays at the K-absorption edge of bromine." Acta Oncologica. 35(7). 877-882 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hieda, T.Hirono, A.Azami, M.Suzuki, Y.Furusawa, H.Maezawa, N.Usami, A.Yokota, K.Kobayashi: "Single- and double-strand breaks in pBR322 plasmid DNA by monochromatic X-rays on and off the K-absorption peak of phosphorus." Int.J.Radiation Biol.70(4). 437-445 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, M.Watanabe, T.Kanai, Y.Kase, F.Yatagai, T.Kato and S.Matsubara: "LET dependence of cell death, mutation induction and chromatin damage in human cells irradiated with accelerated carbon ions." Advances in Space Research. 18. 127-136 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Uehara, M.Miyoshi, K.Andou, S.Koike, K.Masuda: "Early skin shrinkage, late skin contraction and leg contracture of mice exposed to two equal fractions of neutron" J.Jpn.Soc.Ther.Radiol.Oncol.8. 21-27 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Nomura, Y.Nakata, T.Inoue, A.Uzawa, S.Itamura, K.Nerome, M.Akashi and G.Suzuki: "In vivo induction of cytotoxic T lymphocutes specific for a single epitope introduced into an unrelated molecule." J.Immunol.Methods. 193. 41-49 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Akashi, S.Takagi and M.Hachiya: "Anti-cancer agent OK432 induces manganese superoxide dismutase in human granulocytes." Int.J.Cancer. 68. 384-390 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Shiohara, M.Akashi, A.F.Combart, R.Yang and H.P.Koeffler: "Tumor necrosis factor a : Posttranscriptional stabilization of WAF1 mRNA in p53-deficient human leukemic cells." J.Cellular Physiology. 166. 568-576 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Yamada and K.Ando: "The role of topoisomerase II in multidrug resistance." in Multidrug resistance in cancer cells. ed.by S.Gupta and T.Tsuruo. John Wiley & Sons Ltd., CHichester. 137-149 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Maezawa, M.Suzuki, A.Yokoya, N.Usami, K.Kobayashi: "Repair of chromatin breaks produced by monochromatic X-rays with energies of around K-shell absorption edge of phosphorus in V79 cells." Photon Factory Activity Rep.No.14. 420 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Iizuka, K.Ando, T.Aruga, H.Itsukaichi, K.Fukutsu, H.Nagasawa and H.Moriya: "Effects of reoxygenation on repair of potentially lethal radiation damage in cultured MG-63 osteosarcoma cells" Radiation Research. 147. 179-184 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kumiko Fukutsu, Tatsuaki Kanai, Yoshiya Furusawa and Koichi Ando: "Response of Mouse Intestine after Single and Fractionated Irradiation of Accelerated Carbon Ions with a Spread-Out Bragg Peak" Radiation Research. 148. 168-174 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Murakami, H.Tsujii, Y.Furusawa, K.Ando, T.Kanai, S.Yamada, K.Kawachi: "Medical and other applications of high-energy heavy-ion beams from HIMAC" Journal of Nuclear Materials. 248. 360-368 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Hachiya, S.Shimizu, Y.Osawa and M.Akashi: "Endogeneous production of tumour necrosis factor is required for manganese superoxide dismutase expression by irradiation in the human monocytic cell line THP-1" Biochem.J.328. 615-623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, Y.Kase, T.Kanai, F.Yatagai and M.Watanabe: "LET dependence of cell death and chromatin-break induction in normal human cells irradiated by neon-ion beams." International Journal of Radiation Biology. 72. 497-503 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Akashi and H.P.Koeller: "Li-Fraumeni syndrome and the role of the p53 tumor suppressor gene in cancer susceptability." Clinical Obster. Gynecol.4(1). 172-199 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, M.Watanabe, Y.Kase, T.Kanai and F.Yatagai: "LET dependence of cell death, mutation induction and chromosome damage irradiated by accelerated carbon ions." Solar-Terrestrial Predictions-V,Proceedings of a Workshop at Hitachi. 486-494 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki, Y.Kase, T.Kanai and K.Ando: "Correlation between cell death and non-rejoining PCC breaks by carbon-ion beams." Advances in Space Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ando, S.Koike, K.Nojima, Y-J.Chen, C.Ohira, S.Ando, N.Kobayashi, T.Ohbuchi, W.Shimizu and T.Kanai: "Mouse skin reactions following fractionated irradiation with carbon ions." Int.J.Radiation Biology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Suzuki,Y.Kase,T.Kanai,F.Yatagai and M.Watanabe,: "LET dependence of cell death and chromatin-break induction in normal human cells irradiated by neon-ion beams." International Journal of Radiation Biology. 72. 497-503 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kumiko Fukutsu,Tatsuaki Kanai,Yoshiya Furusawa and Koichi Ando: "Response of Mouse Intestine after Single and Fractionated Irradiation of Accelerated Carbon Ions with a Spread-Out Bragg Peak." Radiation Research. 148. 168-174 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ando,S.Koike,K.Nojima,Y-J.Chen,C.Ohira,S.Ando,N.Kobayashi,T.Ohbuchi,W.Shimizu and T.Kanai: "Mouse skin reactions following fractionated irradiation with carbon ions." Int.J.Radiation Biology. in press. (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M Akashi,HP Koeffler.: "Li-Fraumeni syndrome and the role of the p53 tumors uppressor gene in cancer susceptibility." Clin.Obst.Gynecol.41. 172-199 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] M Hachiya,S Shimizu,Y Osawa,M Akashi.: "Endogenous production of tumor necrosis factor is required for manganese superoxide dismutase expression in the human monocytic cell line THP-1." Biochem J. 328. 615-623 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鈴木雅雄: "クロマチン損傷と放射線感受性の相関性" Japanese Journal of Cancer Clinics. 43(2). 156-162 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Suzuki,Y.Kase,T.Kanai and K.Ando: "Correlation between cell death and induction of non-rejoining PCC breaks by carbon-ion beams." Advances in Space Research. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Akashi,Sayoko Takagi and Misao Hachiya: "Anti-cancer agent OK432 induces manganese superoxide dismutase in human granulocytes." Int.J.Cancer. 68. 384-390 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Uehara,M.Miyoshi,K.Andou,S.Koike,K.Masuda: "Early skin shrinkage,late skin contraction and leg contracture of mice exposed to two equal fractions of neutron." J.Jpn.Soc.Ther.Radiol.Oncol. 8. 21-27 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Namba,T.Irie,K.Fukushi,M.Iyo,T.Hashimoto and K.Ando: "Time courses of changes in cerebral blood flow and blood-brain barrier integrity by focal proton radiation in the rat." Neurological Research. 18. 83-86 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Iizuka,K.Ando,T.Aruga,H.Itsukaichi,K.Fukutsu,H.Nagasawa and H.Moriya: "Effects of reoxygenation on repair of potentially lethal radiation damage in cultured MG-63 osteosarcoma cells." Radiation Research. 147. 179-184 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 安藤興一: "がんに克つ驚異のHIMAC" ミオシン出版(森田晧三編), 58-68 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Yamada and K.Ando: "Multidrug resistance in cancer cells" John Wiley & Sons Ltd.(ed.by S.Gupta and T.Tsuruo), 137-149 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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