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Studies on cytokines and proteases which regulate UV-induced mutation in human cells

Research Project

Project/Area Number 09680516
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 InstitutionChiba University

Principal Investigator

SUZUKI Nobuo  Chiba Univ.Med.Biochemi., Professor, 医学部, 教授 (90111426)

Co-Investigator(Kenkyū-buntansha) HIWASA Takaki  Chiba Univ.Med.Biochemi., Assistant, 医学部, 助手 (30260251)
ISHIJIMA Sumio  Kyoto Pref.Univ.Dept.Agric., Assoc.Professor, 農学部, 助教授 (70184520)
高橋 俊二  千葉大学, 医学部, 助手
野村 純  千葉大学, 医学部, 助手 (30252886)
喜多 和子  千葉大学, 医学部, 助手 (80302545)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordshuman cells / ultraviolet ray / mutation / cytokine / protease
Research Abstract

In order to clarify molecular mechanisms which regulate mutability in UV(mainly 250nm wavelength) - irradiated human cells, particularly those regulated by proteases and cytokines.
1. Partial purification and characterization of UV-induced proteases were preformed and protease samples were obtaind from cell lysates of variant cells with increased levels of the induced protease activity. The samples contained molecules with about 20,000 Mr, the activity of which is inhibited by antipain but enhanced by ALLNa1.
2. Using PCR-differential display, we have searched for genes expressed specifically in human interferon (HuIFN)- beta -treated Cockayne syndrome (CS) fibroblast cells. The cDNAs of six clones were similar to expression tagged sequences from unknown genes in databases and the remaining one was identical to the cDNA of the xeroderma pigmentosum XPG gene. Together with our previous finding of increased resistance to ultraviolet (UV) cell-killing of CS cells pretreated with HuIFN- beta … More prior to UV irradiation, suggest that XPG might be one of the genes possibly involved in the HuIFN- beta-induced UV-resistance.
3. UV-resistant UV'-10 cells were established from UV-sensitive human RSb cells. We searched here for genes expressed differentially between UV'-10 and RSb cells using a differencial display method to elucidate the molecular mechanisms underlying the UV-resistance. Thirteen candidate cDNA fragment were obtained from 514 mRNA species first screened. Among the cDNA fragments, 3 revealed increased mRNA expression in UV'-10 cells compared with RSb cells by Northern analysis. Nucleotide sequence analysis identified 2 of the 3 cDNA fragments as encoding nucleophosimin (NPM) and T-plastin. The expression of NPM mRNA was induced after UV irradiation in UV'-10 cells but not in RSb cells, whereas irradiation did not affect the expression of T-plastin mRNA.UV'-10 cells transfected with antisense cDNA for NPM mRNA and possibly T-plastin genes may contribute to the incresed resistance to UV cell-killing, at least in the human cells tested. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Suzuki, N., et al.: "UV-induced mutations affecting codon12 of the K-ras gene are suppressed by interferon-α in human Rsa cells" Mutation Research. 373. 251-256 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujii, K., et al.: "Abnormal DNA synthesis activity induced by X-rays in nevoid basal cell carcinoma syndrome cells" Biochem.Biophys.Res.Commun.240・2. 269-272 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 鈴木 信夫: "ストレス感受性突然変異促進因子" BIO INDUSTRY. 14・4. 5-9 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 鈴木 信夫: "ストレスがもたらす万病のもとを求めて一新しく見出したSF-EPA・SF-Xネットワークから予測される生態機能システムの破綻" 千葉医学. 73. 61-65 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miura, N., et al.: "Establishment of a new human megakaryoblastic cell line, CMY, with chromosome 17p abnormalities" Int.J.Mol.Med.1. 559-563 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Isogai, E., et al.: "Protease activation following UV irradiation is linked to hypomutability in human cells selected for resistance to combination of UV and antipain" Mutation Res.403. 215-222 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sugita, K., et al.: "Enhancement of XP-G mRNA expression by human interferon-b in Cockayne syndrome cells" Mutation Res.408. 67-72 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki, H., et al.: "Mutagenicity of microcystin-LR in human RSa cells" Int.J.Mol.Med.2. 109-112 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, Y., et.al: "Search for genes involved in UV-resistance in human cells by mRNA differential display : increased transcriptional expression of nucleophosmin and T-plastin genes in association with the resistance" Biochem.Biopys.Res.Commun.248. 597-602 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki, N., et al.: "Detection of Serum Factors Enhancing Cell Mutability From Lung Cancer Patients by Application of Hypermutable Human Rs Cells" Int.J.Cancer. 78. 550-555 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wu, Y., et al.: "Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line" Int.J.Oncol.13. 1241-1245 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kikuno, K., et al.: "Search for genes responsible for UV susceptibility of human cells : involvment of syndecan-1 in UV resistance" Biochem.Biophys.Res.Commun.253. 519-523 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujii, K., Suzuki, N., Kita, K., Ishijima, S,Sonoda, T., Dezawa, M., Sugita, K.and Niimi, H.: "Abnormal DNA synthesis activity induced by X-rays in nevoid basal cell carcinoma syndrome cells." Biochem.Biophys.Res.Commun.240. 269-272 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki, N., Suzuki, H., Ishizuka, T., Yamamori, H.and Ino, H.: "UV-induced mutations affecting codon12 of the K-ras gene are suppressed by interferon-alpha in human Rsa cells." Mutation Research. 373. 251-256 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Isogai, E,Ishijima, S., Sonoda, T., Kita, K., Suzuki, H., Hasegawa, R., Yamamori, H., Takakubo, Y., and Suzuki, N.: "Protease activation following UV irradiation is linked to hypomutability in human calls selected for resistance to combination of UV and antipain" Mutation Res.403. 215-222 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sugita, K,Suzuki, N., Higuchi, Y., Kita, K., Suzuki, Y., and Lehmann, A.: "Enhancement of XP-G mRNA expression by human interferon-beta in Cockayne syndrome cells." Mutation Res.408. 67-72 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki, H,Watanabe, M., Wu, Y., Sugita, T., Kita, K., Sato, T., Wang, X., Tanzawa, H., Sekiya, S.and Suzuki, N.: "Mutagenicity of microcystin-LR in human RSa cells." Int.J.Mol.Med.2. 109-112 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, Y,Kita, K., Nakanishi, H., Wang, XL., Sugaya, S., Tanzawa, H., Yamamori, H., Sugita, K., Yamamura A.and Suzuki, N.: "Search for genes involved in UV-resistance in human cells by mRNA differential display : increased transcriptional expression of nucleophosmin and T-plastin genes in association with the resistance." Biochem.Biophys.Res.Commun.248. 597-602 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki, N., Ishibashi, M., Kita, K., Wu, Y., Nomura, J., Takakubo, Y., Hiroshima, K., Genga, K., Ohwada, H.and Hayashi, Y.: "Detection of Serum Factors Enhancing Cell Mutability From Lung Cancer Patients by Application of Hypermutable Human RS Cells." Int.J.Cancer. 78. 550-555 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wu, Y., Hiwasa, T,Isogai, E., Sonoda, T., Kita, K., Chen, Z., Sugaya, S., Yamamori, H., Takazawa, H.and Suzuki, N.: "Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line" Int.J.Oncol.13. 1241-1245 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kikuno, K., Kita, K., Nomura, J., Hiwasa, T., Yonemitsu, H.and Suzuki, N.: "Search for genes responsible for UV susceptibility of human cells : involvment of syndecan-1 in UV resistance." Biochem.Biophys.Res.Commun.253. 519-523 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miura,N.,et al.: "Establishment of a new human megakaryoblastic cell line,CMY,with chromosome 17p abnormalities" Int.J.Mol.Med.1. 559-563 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Isogai,E.,et al.: "Protease activation following UV irradiation is linked to hypomutability in human cells selected for resistance to combination of UV and antipain" Mutation Res.403. 215-222 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugita,K.,et al.: "Enhancement of XP-G mRNA expression by human interferon-b in Cockayne syndrome cells" Mutation Res.408. 67-72 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,H.,et al.: "Mutagenicity of microcystin-LR in human RSa cells" Int.J.Mol.Med.2. 109-112 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Higuchi,Y.,et al.: "Search for genes involved in UV-resistance in human cells by mRNA differential display:increased transcriptional expression of nucleophosmin and T-plastin genes in association with the resistance" Biochem.Biopys.Res.Commun.248. 597-602 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,N.,et al.: "Detection of Serum Factors Enhancing Cell Mutability From Lung Cancer Patients by Application of Hypermutable Human Rs Cells" Int.J.Cancer. 78. 550-555 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wu,Y.,et al.: "Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line" Int.J.Oncol.13. 1241-1245 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kikuno,K.,et al.: "Search for genes responsible for UV susceptibility fo human cells:involvment of syndecan-1 in UV resistance" Biochem.Biophys.Res.Commun.253. 519-523 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,N: "UV-induced mutations affecting codon12 of the K-ras gene are suppressed by interferon-α in human Rsa cells" Mutation Res.373. 251-256 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,K: "Abnormal DNA synthesis activity induced by X-rays in nevoid basal cell carcinoma syndrome cells" Biochem.Biophys.Res.Commun.240・2. 269-272 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miura,N: "Establishment of a new human megakaryoblastic cell line,CMY,with chromosome 17p abnormalities" Int.J.Mol.Med.(印刷中)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鈴木信夫: "ストレスがもたらす万病のもとを求めて--新しく見出したSF-EPA・SF-Xネットワークから予測される生体機能" 千葉医学. 73. 61-65 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鈴木信夫: "ストレス感受性突然変異促進因子" BIO INDUSTRY. 14・4. 5-9 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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