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Study of effects of oxidative stress on tumorigensis in LEC rats that shows a high incidence of spontaneous liver cancer.

Research Project

Project/Area Number 10660289
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionRakuno Gakuen University

Principal Investigator

HAYASHI Masanobu  Rakuno Gakuen University, School of Veterinary Medicine, Professor, 獣医学部, 教授 (10130337)

Co-Investigator(Kenkyū-buntansha) ENDOH Daiji  Rakuno Gakuen University, School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (40168828)
荒井 惣一郎  酪農学園大学, 獣医学部, 助教授 (40151138)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordstumorigenesis / Oxidative stress / DNA lesion / Cell cycle / LEC rat / Radiosensitivity / DNA依存プロテインキナーゼ
Research Abstract

We investigated effects of oxidative stress on tumorigensis in LEC rats that shows a high incidence of spontaneous liver cancer.
1. Although copper and iron accumulated in the liver of LEC rats in an age-dependent manner, we showed that copper accumulation in the liver of LEC rats induced DNA strand breaks, but accumulation of iron did not.
2. The slow repair of potentially lethal damage (PLD) occurred in LEC rat cells but not the fast repair of PLD.Wortmannin, an inhibitor of DNA-dependent protein kinase (DNA-PK) enhances the radiosensitivity of control rat cells but not that of LEC rat cells. Although oxidative stress produces a variety of lesions in DNA, double-strand breaks (DSBs) appear to be responsible for most oxidative stress-induced cell death. Repair of DSBs plays an important role in the fixation of fast-repairing PLD.DNA-PK that is a heterotrimeric complex comprised of two components : a large catalytic subunit (DNA-PKcs) and DNA-targeting component (Ku 70 and Ku 80). In the control cells Ku proteins accumulated in the nucleus after production of DSBs, but did not in LEC rat cells.
3. LEC rat cells showed an abnormal accumulation of G2/M-phase cells after treatment with oxidative stress at S phase. LEC rat cells also showed a higher sensitivity to induction of apoptosis after treatment of the cells with a variety of stress.
These results suggest that a deficiency of DSBs repair and an abnormality of some signal transduction pathways following oxidative stress may be associated with a high incidence of liver cancer of LEC rats.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] M.Hayashi: "Higher sensitivity in induction of apoptosis in fibroblast cell lines derived from LEC strain rats to UV-irradiation."J.Vet.Med.Sci.. 60. 207-212 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Endoh: "Retroviral sequence located in border region of short unique region and short terminal repeat of Md5 strain Marek's disease virus type 1."J.Vet.Med.Sci.. 60. 227-235 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Inhibitory effects of modified oligonucleotides complementary to the leader RNA on the multiplication of mouse hepatitis virus."Adv.Exp.Med.Biol.. 440. 693-695 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Intramuscular injection of plasmid DNA expressing mRNA7 coding the nucleocapsid protein of JHMV partially protected mice acute infection with JHMV."Adv.Exp.Med.Biol.. 440. 701-705 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Higher sensitivity in LEC rat cells to a topoisomerase II inhibitor, ellipticine."J.Vet.Med.Sci.. 60. 969-971 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Antisense oligonucleotide complementary to the BamHI-H gene family of Marek's disease virus induced growth arrest of MDCC-MSB1 cells in the S-phase."J.Vet.Med.Sci.. 61. 389-394 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Abnormal accumulation of G2/M-phase cells from LEC strain rats after X-irradiation at S phase."J.Vet.Med.Sci.. 61. 975-978 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Okui: "Deficiency of fast repair process of potentially lethal damage induced by X-irradiation in fibroblasts derived from LEC strain rats."Mutat.Res.. 435. 81-88 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Expression of protein gene product 9.5, a neuronalubiquitin C-terminal hydrolase, and its developing change in sertoli cells of mouse testis."Mol.Reprod.Dev.. 54. 333-341 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Renin in exocrine glands of different mouse strains."Anat.Histol.Embryol.. 28. 239-242 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Metaphase-specific cell death in mitotic spermatocytes in mice."Cell Tissue Res.. 296. 359-369 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.O.Chao: "Seropretvalence of bovine immunodeficiency virus in dairy and beef cattle herds in Korea."J.Vet.Med.Sci.. 61. 549-551 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Expression of angiotensinogen in the uterus induced by coagulating gland rennin in mice."Anat.Histol.Embryol.. 28. 119-124 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Arai: "Effects of antioxidants on induction of apoptosis in bursal cells of Fabricius during in vitro cultivation."J.Vet.Med.Sci.. 62. 43-47 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Wortmannin, a radiation sensitizer, enhances the radiosensitivity of WKAH rat cells but not that of LEC rat cells."J.Vet.Med.Sci.. 62. 191-194 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Arai: "Inhibitory effects of long-wave ultraviolet radiation of isolated chicken liver nuclei on the Mg^<2+>-dependent transition of chromatin structure."J.Vet.Med.Sci.. 62. 861-865 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Hepatic copper accumulation induces DNA strand breaks in the liver cells of Long-Evans Cinnamon (LEC) strain rats."Biochem.Biophys.Res.Commun.. 276. 174-178 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Endoh: "Application of representational difference analysis to genomic fragments of Marek's disease virus."J.Clinical Microbiol.. 38. 4310-4314 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Arai: "Effects of lonb-wave ultraviolet (UVA) radiation on MgCl2-dependent structural transition of chromatin in isolated chicken liver nuclei."J.Rakuno Gaknen Univ.. 25. 19-24 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Endoh: "Hypertonic treatment inhibits radiation-induced nuclear translocation of the proteins G22p1 (Ku70) and Xrcc5 (Ku80) in rat fibroblasts."Radiat.Res.. 155. 320-327 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Higher sensitivity in induction of apoptosis in fibroblast cell lines derived from LEC strain rats to UV-irradiation"J.Vet.Med.Sci.. 60 (2). 207-212 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Endoh: "Retroviral sequence located in border region of short unique region and short terminal repeat of Md5 strain of Marek's disease virus type 1"J.Vet.Med.Sci.. 60 (2). 227-235 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Inhibitory effects of modified oligonucleotides complementary to the leader RNA on the multiplication of mouse hepatitis virus"Adv.Exp.Med.Biol.. 440. 701-705 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Intramuscular injection of plasmid DNA expressing mRNA7 coding the nucleocapsid protein of JHMV partially protected mice against acute infection with JHMV"Adv.Exp.Med.Biol.. 440. 693-695 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Higher sensitivity in LEC rat cells to a topoisomerase II inhibitor, ellipticine"J.Vet.Med.Sci.. 60 (8). 969-971 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Antisense oligonucleotide complementary to the BamHI-H gene family of Marek's disease virus induced growth arrest of MDCC-MSB 1 cells in the S-phase."J.Vet.Med.Sci.. 61 (4). 389-394 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Abnormal accumulation of G2/M-phase cells from LEC strain rats after X-irradiation at S Phase."J.Vet.Med.Sci.. 61 (8). 975-978 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Okui: "Deficiency of fast repair process of potentially lethal damage induced by X-irradiation in fibroblasts derived from LEC strain rats"Mut.Res.. 435 (1). 81-88 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Expression of protein gene product 9.5, a neuronalubiquitin C-terminal hydrolase, and its developing change in sertoli cells of mouse testis"Mol.Reprod.Dev.. 54 (3). 333-341 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Renin in exocrine glands of different mouse strains"Anat.Histol.Embryol.. 28 (2). 239-242 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kon: "Metaphase-specific cell death in mitotic spermatocytes in mice"Cell Tissue Res.. 296 (3). 359-369 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.O.Chao: "Seropretvalence of bovine immunodeficiency virus in dairy and beef cattle herds in Korea"J.Vet.Med.Sci.. 61 (4). 549-551 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Arai: "Effects of antioxidants on induction of apoptosis in bursal cells of Fabricius during in vitro cultivation"J.Vet.Med.Sci.. 62 (1). 43-47 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Wortmannin, a radiation sensitizer, enhances the radiosensitivity of WKAH rat cells but not that of LEC rat cells"J.Vet.Med.Sci.. 62 (2). 191-194 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Arai: "Inhibitory effects of long-wave ultraviolet radiation of isolated chicken liver nuclei on the Mg^<2+>-dependent transition of chromatin structure"J.Vet.Med.Sci.. 62 (8). 861-865 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Hepatic copper accumulation induces DNA strand breaks in the liver cells of Long-Evans Cinnamon (LEC) strain rats"Biochem. Biophys. Res. Commun.. 276 (1). 174-178 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Endoh: "Application of representational difference analysis to genomic fragments of Marek's disease virus"J.Clin.Microbiol.. 38 (10). 4310-4314 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] D.Endoh: "Hypertonic treatment inhibits radiation-induced nuclear translocation of Ku proteins in rat fibroblasts"Radiat.Res.. 155 (1). 320-327 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Arai: "Effects of long-wave ultraviolet (UVA) radiation on the MgCl_2-dependent structure transition of chromatin in isolated chicken liver nuclei"J.Rakuno.Gakuen Univ.. 25 (1). 19-24 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Hayashi: "Wortmannin, a radiation sensitizer, enhances the radiosensitivity of WKAH rat cells but not that of LEC rat cells."J.Vet.Med.Sci.. 62・1. 191-194 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Arai: "Inhibitory effects of long-wave ultraviolet radiation of isolated chicken liver nuclei on the Mg^<2+>-dependent transition of chromatin structure."J.Vet.Med.Sci.. 62・8. 861-865 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Hayashi: "Hepatic copper accumulation induces DNA strand breaks in the liver cells of Long-Evans Cinnamon (LEC) strain rats."Biochemical.Biopysical.Res.Commun.. 276・1. 174-178 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] D.Endoh: "Application of representational difference analysis to genomic fragments of Marek's disease virus."J.Clinical Microbiol.. 38・12. 4310-4314 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Arai: "Effects of lonb-wave ultraviolet (UVA) radiation on MgCl2-dependent structural transition fo chromatin in isolated chicken liver nuclei."J.Rakuno Gakuen Univ.. 25・1. 19-24 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] D.Endoh: "Hypertonic treatment inhibits radiation-induced nuclear translocation of the proteins G22pl(Ku70) and Xrcc5(Ku80) in rat fibroblasts."Radiat.Res.. 155・1. 320-327 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Hayashi: "Antisense oligonucleotide complementary to the BamHI-H gene family of Marek's disease virus induced growth arrest of MDCC-MSB1 cells in the S-phase."J.Vet.Med.Sci. 61(4). 389-394 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Hayashi: "Abnormal accumulation of G2/M-phase cells from LEC strain rats after X-irradiation at S phase."J.Vet.Med.Sci.. 61(8). 975-978 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Okui: "Deficiency of fast repair process of potentially lethal damage induced by X-irradiation in fibroblasts derived from LEC strain rats."Mut.Res.. 435(1). 81-88 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Arai: "Effects of antioxidants on induction of apoptosis in bursal cells of Fabricius during in vitro cultivation."J.Vet.Med.Sci. 62(1). 43-47 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Hayashi: "Wortmannin,a radiation sensitizer,enhances the radiosensitivity of WKAH rat cells but not that of LEC rat cells."J.Vet.Med.Sci. 62(2). 191-194 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Hayashi: "Higher sensitivity in induction of apoptosis in fibroblast cell lines derived from LEC strain rats to UV-irradiation." J.Vet.Med.Sci.60・2. 207-212 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] D.Endoh: "Retroviral seguence located in border region of short uniqne region and short terminal repent of M4.5 strain of Hurek's disease rirastylel." J.Vet.Med.Sci.60・2. 227-235 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Hayashi: "Higher sesitivity in LEC rat cells to topoisomeruseII inhibitor,ellipticine." J.Vet.Med.Sci.60・8. 969-971 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 林 正信: "放射線感受性モデル動物としてのLECラットについて" 放射線生物研究. 33・2. 123-136 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Hayashi: "Intramuscular injection of plasmid DNA expressing mRNA coding the nucleocapsid protein of JHMV partially proteoted mice against acuteinifection with JHMV." Adv.Exp.Med.Biol.440. 693-695 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Hayashi: "Inhibitory effects of nodifiod oliyonacleotides complementary to the leuder RNA on the multiplication of mouse hepatitis virus." Adv.Exp.Med.Biol.440. 701-705 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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