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The Total Amount of DNA Damage Determines Ultraviolet-Radiation-Induced Cytotoxicity after Uniform- or Localized Irradiation of Human Cells

Research Project

Project/Area Number 13680632
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionNara Medical University

Principal Investigator

MORI Toshio  Nara Medical University, Medicine, Associate professor, 医学部, 助教授 (10115280)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsUV / cyclobutane pyrimidine dimer / (6-4) photoproduct / micropore UV irradiation / apoptosis / nucleotide excision repair / DNA damage / Cockayne syndrome / UVC / マイクロビーム / ミクロブタン型ダイマー / 6-4型ダイマー / UV / 紫外線局所照射 / 色素性乾皮症 / XP / PCNA
Research Abstract

We have recently developed a micropore ultraviolet (UV) irradiation technique. An isopore membrane filter with 3μm diameter pores shields UVC radiation from cultured human fibroblasts, leading to partial irradiation within the cells with an average of about 3 exposed areas per nucleus. The present study addressed the question of whether the spatial distribution of DNA damage within a cell nucleus is important in triggering UV-induce cytotoxicity. We have examined whether there are differences incytotoxicity between partially UV-irradiated cells and uniformly irradiated cells after equal amounts of DNA damage were induced in the cell nuclei. We first determined DNA damage formation in normal human fibroblasts using anenzyme-linked immunosorbent assay. We found that 5 J per m^2 UV irradiation produced an equivalent amount of cyclobutane pyrimidine dimers and (6-4) photoproducts per cell as 100 J per m^2 with the membrane filter shield. At those doses, we found that both types of UV irradiation induced similar levels of cytotoxicity as assessed by an MTS assay. Both types of UV irradiated cells also had similar cell-cycle distribution and apoptosis as measured by flowcytometry. Moreover, no significant differences in repair kinetics for either type of photolesion were observed between the two different UV treatments. Similar results were obtained in Cockayne syndrome cells that are defective in transcription-coupled nucleotide excision repair Present results indicate that in the range of photoproducts studied, the spatial distribution of DNA damage within a cell is less important than the amount of damage in triggering UV-induced cytotoxicity.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] K.Imoto et al.: "The Total Amount of DNA Damage Determines Ultraviolet-radiation-induced Cytotoxicity After Uniform or Localized Irradiation of Human Cells"J.Invest.Dermatol.. 119. 1177-1182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] R.Takimoto et al.: "BRCA1 transcriptionally regulates damaged"Cancer Biol.Ther.. 1. 177-186 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Wakasugi et al.: "DDB Accumulates at DNA Damage Sites Immediately after UV Irradiation and Directly Stimulates Nucleotide Excision Repair"J.Biol.chem.. 277. 1637-1640 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Akiyama et al.: "Antitumor effects induced by dendritic cell-based immunotherapy against established pancreatic cancer in hamsters"Cancer Lett.. 184. 37-47 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Mori, N.Kobayashi: "Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies"J.Nara Med.Assoc.. 53. 179-191 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Katsumi et al.: "In situ visualization of ultraviolet light-induced DNA damage reparirin locally irradiated human fibroblasts"J.Invest.Dermatol.. 117. 1156-1161 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 花岡, 武田, 柴田編: "ゲノムの修復と組換え-原子レベルから疾患まで-"シュプリンガー・フェアラーク東京. 161 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Imoto, N.Kobayashi, S.Katsumi, Y.Nishiwaki, T.Iwamoto, A.Yamamoto, Y.Yamashina, T.Shirai, S.Miyagawa, Y.Dohi, S.Sugiura and T.Mori: "The total amount of DNA damage determines ultraviolet-radiation-induced cytotoxicity after uniform- or localized irradiation of human cells"J.Invest.Dermatol.. 119. 1177-1182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] R.Takimoto, T.K.MacLachlan, D.T.Dicker, Y.Niitsu, T.Mori and W.S.El-Deiry: "BRCA1 transcriptionally regulates damaged DMA binding protein (DDB2) in the DNA repair response following UV-irradiation"Cancer BiolTher. 1. 177-186 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Wakasugi, A.Kawashima, H.Morioka, S.Linn, A.Sancar, T.Mori, O.Nikaido and T.Matsunaga: "DDB accumulates at DNA damage sites immediately after UV irradiation and directly stimulates nucleotide excision repair"J.Biol.Chem.. 277. 1637-1640 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Akiyama, K.Maruyama, N.Nara, T.Hojo, J-Y Cheng, T.Mori, R.H.Wiltrout and K.Yamaguchi: "Antitumor effects induced by dendritic cell-based immunotherapy against established pancreatic cancer in hamsters"Cancer Lett.. 184. 37-47 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Mori and N.Kobayashi: "Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies"J.Nara Med.Assoc.. 53. 179-191 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Katsumi, N.Kobayashi, K.Imoto, A.Nakagawa, Y.Yamashina, T.Muramatsu, T.Shirai S.Miyagawa, S.Sugiurg. F.Hanaoka, T.Matsunaga, O.Nikaido and T.Mori: "In situ visualization of ultraviolet light-induced DNA damage repair in locally irradiated human fibroblasts"J.InvestDermatol. 117. 1156-1161 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Kubota, C.Niwa, T.Ohnuma, Y.Ohko, T.Tatsuma, T.Mori and A.Fujishima: "Protective effect of TiO2 particles on UV light induced pyrimidine dimer formation"J.Photochem.Photobiol.A : Chemistry. 141. 225-230 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Kobayashi, S.Katsumi, K.Imoto, A.Nakagawa, S.Miyagawa, M.Furumura and T.Mori: "Quantitation and visualization of ultraviolet-induced DMA damage using specific antibodies : Application to pigment cell biology"Pigment Cell Res.. 14. 94-102 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Yanase, H.Ando, M.Horikawa, M.WatanabeT.Mori and N.Matsuda: "Possible involvement of ERK1/2 in UVA-induced melanogenesis in cultured normal human epidermalmelanocytes"Pigment Cell Res.. 14. 103-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K, Imoto et al.: "The Total Amount of DNA Damage Determines Ultraviolet-radiation-induced Cytotoxicity After Uniform or Localized Irradiation of Human Cells"J. Invest. Dermatol.. 119. 1177-1182 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R, Takimoto et al.: "BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation"Cancer Biol. Ther.. 1. 177-186 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M, Wakasugi et al.: "DDB Accumulates at DNA Damage Sites Immediately after UV Irradiation and Directly Stimulates Nucleotide Excision Repair"J. Biol. Chem.. 277. 1637-1640 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y, Akiyama et al.: "Antitumor effects induced by dendritic cell-based immunotherapy against established pancreatic cancer in hamsters"Cancer Lett.. 184. 37-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T, Mori, N, Kobayashi: "Quantization and visualization of ultraviolet・・・"J. Nara Med Assoc.. 53. 179-191 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S, Katsumi et al.: "In Situ Visualization of Ultraviolet-Light-Induced DNA Damage Repair in Locally Irradiated Human Fibroblasts"J. Invest. Dermatol.. 117. 1156-1161 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 花岡文雄: "ゲノムの修復と組換え-原子レベルから疾患まで-"シュプリンガー・フェアラーク東京(株). 161 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Wakasugi et al.: "DDB accumulates at DNA damage sites immoderately"J. Biol. chem.. 277. 1637-1640 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Katumi et al.: "Insitu Visualization of ultraviolet-light-induced"J. Invest. Dermatol. 117. 1156-1161 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Kobayashi et al.: "Quantitation and Visualization of ultraviolet"Pigment Cell Res.. 14. 94-102 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Yanase et al.: "Possible involvement of ERK 1/2 in UVA-induced"Pigment Cell Res.. 14. 103-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Kubota et al.: "Protective effect of TiO_2 particles on UV light"J. Photochem. Photobiol. A : Chemistry. 141. 225-230 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] E.Otoshi et al.: "Respective roles of cyclobutane pyrimidine"Cancer Res.. 60. 1729-1735 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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