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Analyses for Genes Controlling Susceptibility to Radiation-Induced Tumorigenesis

Research Project

Project/Area Number 14580571
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 InstitutionOsaka Prefecture University

Principal Investigator

MORI Nobuko  Osaka Prefecture University, Res.Inst.Advan.Sci. & Technol., Assistant Professor, 先端科学研究所, 講師 (90100221)

Co-Investigator(Kenkyū-buntansha) OKUMOTO Masaaki  Osaka Prefecture University, Res.Inst.Advan.Sci. & Technol., Professor, 先端科学研究所, 教授 (50100186)
YAMATE Jyoji  Osaka Prefecture University, Grad.Sc.Agri.Biol.Sci., Associate Professor, 大学院・農学生命科学研究科, 助教授 (50150115)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordslymphoma / radiation carcinogenesis / tumor susceptibility / mouse / genetic analysis / 発癌感受性 / 乳腺腫瘍 / 放射線発癌 / P53
Research Abstract

(1)Genome-wide screening for tumor susceptibility in [(BALB/c x STS)F1 x STS] mice subjected to 4 x 1.7 Gy X-irradiation detected no chromosomal segment carrying homozygous STS allele, which could achieve tumor resistance equivalent to that of STS mice. This indicates that resistance to lymphomagenesis in STS mice is not under a single gene control. Suggestive (not significant) linkage was detected in the segment close to Pten on chromosome 19 and at a marker D1Mit14 near the telomere of chromosome 1.
(2)Linkage analysis using [(BALB/c x STS)F1 x BALE/c] mice identified two loci responsible for tumor susceptibility on chromosome 4, where the STS allele conferred resistance to lymphomagenesis (chi square values were more than 15.3). One locus located in the vicinity of D4Mit17 (30 cM distal to the centromere) and nearby D4Mit9, INK4a and b, approximately 10 cM distal to the locus, another locus existed. Analysis of several congenic lines bearing various portions of STS-derived chromosome 4 in the BALB/c background confirmed the presence of a tumor susceptibility gene in a 10 Mb region containing these INK4 family genes. Experiments to confirm the existence of another susceptibility gene for lymphomagenesis are ongoing by using a set of congenic mouse lines.
(3)A single exposure to 4 Gy of X-irradiation induced mammary tumors with a frequency less than that of lymphomas in p53 hemizygous mice with the BALE/c background. Furthermore, in the p53 hemizygous mice 4 times irradiation with an X-ray dose less than 1 Gy at a week interval doubled the mammary tumor frequency in compensation for a reduced incidence of lymphomas. Using a genetic cross between (C57BL/6 x p53 hemizygous BALB/c)F1 and BALB/c linkage analysis for mammary tumor susceptibility is presently under way.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (38 results)

All 2005 2004 2003 2002 Other

All Journal Article (27 results) Publications (11 results)

  • [Journal Article] Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice2005

    • Author(s)
      S.Umesako et al.
    • Journal Title

      Breast Cancer Research 7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice.2005

    • Author(s)
      S.Umesako, K.Fujisawa, S.Iiga, N.Mori, M.Takahashi, C.-W.Song, S.Haga, S.Imai, O.Niwa, M.Okumoto
    • Journal Title

      Breast Cancer Res. 7

    • NAID

      130005443074

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice2005

    • Author(s)
      Umesako, S. et al.
    • Journal Title

      Breast Cancer Research 7

      Pages: 164-170

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cisplatin-induced renal interstitial fibrosis in neonatal rats, developing as solitary nephron unit lesions2005

    • Author(s)
      Yamate, J. et al.
    • Journal Title

      Toxicological Pathology 33

      Pages: 207-217

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Allelic Loss Analysis of Lymphomas Induced in Fas-Heterozygous Deficient Mice2004

    • Author(s)
      S.Ogawa et al.
    • Journal Title

      Journal of Veterinary Medicine and Science 66

      Pages: 97-102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hemorrhagic hydrocephalus (hhy) : a novel mutation on mouse chromosome 122004

    • Author(s)
      M.Kuwamura et al.
    • Journal Title

      Developmental Brain Research 152

      Pages: 69-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] X線分割照射したp53ヘテロ欠損BALB/cマウスにおける乳腺腫瘍の高発生2004

    • Author(s)
      森展子, 梅迫誠一 ら
    • Journal Title

      乳癌基礎研究 13

      Pages: 17-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Atmおよびp53ヘテロ欠損マウスの乳癌におけるがん抑制遺伝子領域の解析-9,10,12番染色体における解析2004

    • Author(s)
      飯賀紗代子, 梅迫誠一 ら
    • Journal Title

      乳癌基礎研究 13

      Pages: 29-32

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Atmおよびp53ヘテロ欠損マウスの乳癌におけるがん抑制遺伝子領域の解析-乳癌の発生状況とアリル消失領域のゲノムワイドスクリーニングー2004

    • Author(s)
      梅迫誠一, 飯賀紗代子 ら
    • Journal Title

      乳癌基礎研究 13

      Pages: 33-36

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of lipopolysaccharide on the appearance of macro-phage populations and fibrogenesis in cisplatin-induced rat renal injury2004

    • Author(s)
      J.Yamate, Y.Machida et al.
    • Journal Title

      Experimental Toxicological Pathology 56

      Pages: 13-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of lipopolysaccharide on the appearance of macrophage populations and fibrogenesis in cisplatin-induced rat renal injury.2004

    • Author(s)
      J.Yamate, Y.Machida, M.Ide, M.Kuwamura, O.Sawamoto, J.LaMarre
    • Journal Title

      Exp.Toxicol.Pathol. 56

      Pages: 13-24

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hemorrhagic hydrocephalus (hhy) : a novel mutation on mouse chromosome 12.2004

    • Author(s)
      M.Kuwamura, A.Kinoshita, M.Okumoto, J.Yamate, N.Mori
    • Journal Title

      Dev.Brain Res. 152

      Pages: 69-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Allelic loss analysis of lymphomas induced in Fas-heterozygous deficient mice.2004

    • Author(s)
      S.Ogawa, D.-P.Hong, N.Mori, S.Umesako, C.-W.Song, M.Okumoto
    • Journal Title

      J.Vet.Med.Sci. 66

      Pages: 97-102

    • NAID

      50000389724

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hemorrhagic hydrocephalus (hhy) : a novel mutation on mouse chromosome 122004

    • Author(s)
      Kuwamura, M. et al.
    • Journal Title

      Developmental Brain Research 152

      Pages: 69-72

    • Related Report
      2004 Annual Research Report
  • [Journal Article] X線分割照射したp53ヘテロ欠損BALB/cマウスにおける乳腺腫瘍の高発生2004

    • Author(s)
      森展子 他
    • Journal Title

      乳癌基礎研究 13

      Pages: 17-20

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Atmおよびp53ヘテロ欠損マウスの乳癌におけるがん抑制遺伝子領域の解析-乳癌の発生状況とアリル消失領域のゲノムワイドスクリーニング-2004

    • Author(s)
      梅迫誠一 他
    • Journal Title

      乳癌基礎研究 13

      Pages: 33-36

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of lipopolysaccharide on the appearance of macrophage populations and fibrogenesis in cisplatin-induced rat renal injury2004

    • Author(s)
      Yamate, J.et al.
    • Journal Title

      Exp.Toxicol.Pathol. 56

      Pages: 13-24

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Preferential Induction of Mammary Tumors in p53 Hemizygous BALB/c Mice by Fractionated Irradiation of a Sub-Lethal Dose of X-rays2003

    • Author(s)
      N.Mori, J.Yamate et al.
    • Journal Title

      Journal of Radiation Research 44

      Pages: 249-254

    • NAID

      110002328893

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angioarchitecture of Tumors Induced by Two Different Cloned Cell Lines Established from a Transplantable Rat Malignant Fibrous Histiocytoma2003

    • Author(s)
      I.Tsunenari et al.
    • Journal Title

      Microsc.Microanal. 9

      Pages: 532-541

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angioarchitecture induced by two different cloned cell lines of tumors established from a transplantable rat malignant fibrous histiocytoma.2003

    • Author(s)
      Tsunenari, I., J.Yamate, M.Iwaki, M.Kuwamura, Kotani, S.Sakuma
    • Journal Title

      Microsc.Microanal. 9

      Pages: 532-541

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preferential Induction of Mammary Tumors in p53 Hemizygous BALB/c Mice by Fractionated Irradiation of a Sub-Lethal Dose of X-rays.2003

    • Author(s)
      N.Mori, J.Yamate, S.Umesako, D.-P.Hong, M.Okumoto, R.Nakao
    • Journal Title

      J.Radiat.Res. 44

      Pages: 249-254

    • NAID

      110002328893

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Generation of Large Homozygous Chromosomal Segments by Mitotic Recombination during Lymphomagenesis2002

    • Author(s)
      D.-P.Hong et al.
    • Journal Title

      Journal of Radiation Research 43

      Pages: 187-194

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] SusceptibilityLocifor Radiation Lymphpmagenesis in Mice2002

    • Author(s)
      N.Mori, M.Okumoto
    • Journal Title

      Proc.60^<th> Int.Symposium on Radiation and Homeostasis

      Pages: 439-446

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Putative Tumor-Suppressor Gene Regions Responsible for Radiation Lymphomagenesis in F1 Mice with Different p53 Status2002

    • Author(s)
      D.-P.Hong et al.
    • Journal Title

      Journal of Radiation Research 43

      Pages: 175-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Generation of Large Homozygous Chromosomal Segments by Mitotic Recombination during Lymphomagenesis.2002

    • Author(s)
      D.-P.Hong, K.Kubo, N.Tsugawa, N.Mori, S.Umesako, C.-W.Song, M.Okumoto
    • Journal Title

      J.Radiat.Res. 43

      Pages: 187-194

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Susceptibility Loci for Radiation Lymphomagenesis in Mice.2002

    • Author(s)
      N.Mori, M.Okumoto
    • Journal Title

      Proc.60^<th> Int.Symposium on Radiation and Homeostasis

      Pages: 439-446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Putative Tumor-Suppressor Gene Regions Responsible for Radiation Lymphomagenesis in F1 Mice with Different p53 Status.2002

    • Author(s)
      D.-P.Hong, N.Mori, S.Umesako, C.-W.Song, Y.-G.Park, S.Aizawa, M.Okumoto
    • Journal Title

      J.Radiat.Res. 43

      Pages: 175-185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Mori, N., Yamate, J.et al.: "Preferential induction of mammary tumors in p53 hemizygous BALB/c mice by fractionated irradiation of a sub-lethal dose of X-rays"J.Radiat.Res.. 44. 249-254 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogawa, S. et al.: "Allelic loss analysis of lymphomas induced in Fas-heterozygous Deficient mice."J.Vet.Med.Sci.. 66. 97-102 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakanishi, M. et al.: "Establishment of a transplantable rat pulomnary carcinoma-derived cell-line (IP-B12) as a ne model of humoral hypercarcemia of malignancy and bone metastasis"Tumor Biol.. 24. 70-76 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamate, J et al.: "Characterization of newly-established tumor lines from a spontaneous malignat schwannoma in F344 rats : nerve growth factor production, growth inhibition by transforming growth factor-b1 and macrophage-like phenotype expression."Acta Neuropathol.. 106. 221-233 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori, N. et al.: "Molecular Mechanisms for Radiation-Induced Cellular Response and Cancer Development"Inst.Environ.Sci.(IES). 359 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Mori et al.: "Analyses of susceptibility to radiation-induced tumors : Prkdc, a candidate modifier of lymphomas"Proc. Int. Symposium on Biological Effects of Low Dose Radiation. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Mori, M.Okumoto: "Susceptibility Loci for Radiation Lymphomagenesis in Mice"Proc. 6O^<th> Int. Symposium on Radiation and Homeostasis. 439-446 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] D.-P.Hong et al.: "Putative Tumor-Suppressor Gene Regions Responsible for Radiation Lymphomagenesis in F1 Mice with Different p53 Status"J.Radiat.Res.. 43. 175-185 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] D.-P.Hong et al.: "Generation of Large Homozygous Chromosomal Segments by Mitotic Recombination during Lymphomagenesis"J.Radiat.Res.. 43. 187-194 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawashima, M et al.: "Immunophenotypical changes of neoplastic cells and tumor-associated macro-phages in a rat dendritic cell sarcoma-derived transplantable tumor line (KB-D8)"Virchows Arch.. 442. 141-150 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamate, J et al.: "Establishment and characterization of transplantable tumor line (KB) and cell lines (KB-P and KB-D8) from a rat thymus-derived dendritic cell sarcoma"Virchows Arch.. 440. 616-626 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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