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Study of control mechanisms of gene expression related to colorectal cancer by intestinal flora in rasH2 mice

Research Project

Project/Area Number 12480250
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionThe University of Tokyo

Principal Investigator

ITOH Kikuji  Graduate School of Agriculture and Life Sciences, The University of Tokyo, Assoc. Prof., 大学院・農学生命科学研究科, 助教授 (50100045)

Co-Investigator(Kenkyū-buntansha) ITOH Toshio  Central Inst. of Exp. Anim., Group Director (Researcher), 実験動物中央研究所, 室長(研究職) (20106644)
NAKAYAMA Hiroyuki  Graduate School of Agriculture and Life Sciences, The University of Tokyo, Assoc. Prof., 大学院・農学生命科学研究科, 助教授 (40155891)
平山 和宏  東京大学, 大学院・農学生命科学研究科, 助手 (60208858)
KOBAYASHI Kimio  Central Inst. of Exp. Anim., Group Director (Researcher), 実験動物中央研究所, 室長(研究職) (20205454)
OHNISHI Yasuyuki  Central Inst. of Exp. Anim., Group Director (Researcher), 実験動物中央研究所, 室長(研究職) (70201382)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2000: ¥9,700,000 (Direct Cost: ¥9,700,000)
KeywordsCancer / ras mice / transgenic mice / c-Ha-ras / p53
Research Abstract

1. RasH2 mice harboring human prototype c-Ha-ras genes were injected with 1,2-dimethylhydrazine and examined for mutation and expression levels of human c-Ha-ras, murine Ki-ras, Na-ras and p53. There were no point mutations in these genes. The expression level of transgene mRNA determined by real time RT-PCR was shown to be higher in tumors than in non-tumor colorectal tissues, and expression levels by RT-PCR of murine Ki-ras, Na-ras and p53 in the tumors were no different from those in the non-tumor colorectal tissues.
2. Expression levels of cancer related genes in the tumors and the non-tumor tissues of rasH2 and non-Tg mice were compared using Gene Navigator^<TM> cDNA Array System (TOYOBO). For 11 genes, MMP7, Clusterin, nm23, c-jun, SLC, Bad, Bax, Gelsolin, Ran, SkpI, and p19, expression levels were higher in the tumors than in the non-tumor colorectal tissues in both rasH2 and non-Tg mice.
3. To confirm the high expression levels of 11 genes mentioned above, RT-PCR analysis was performed. Only. MMP7 and Clusterin genes were expressed more in the tumors than in the non-tumor tissues in both rasH2 and non-Tg mice.
4. Expression levels of cancer related genes between tumors and non-tumor tissues in rasH2 mice were similar to those in non-Tg mice.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Ohno, K. et al.: "Inhibitory effect of apple pectin and culture condensate of oifidopacterium・・・・・"Exp. Anim. 49. 305-307 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno, K. et al.: "Effect of bacterial metabolism in the intestine on colorectal tumors induced by・・・・・"J. Exp. Clin. Cancer Res.. 20. 51-56 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Birumachi, J. et al.: "Diesel exhaust-induced air way hyperresponsiveness in c-Ha-ras tramsgenic mice"Toxicol.. 163. 145-152 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Umemura, T. et al.: "Buthylhydrixy to luene (BHT) increases susceptibility of transgenic rasH_2・・・・・"J. Cancer Res. Clin. Oncol.. 127. 583-590 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Maruyama, C. et al.: "Overexpression of human H-ras transgene is responsible for tumors induced・・・・・"Oncol. Reports. 8. 233-237 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohnishi, Y. et al.: "Induction of drug metabolism-related enzymes by methylcholanthrene and・・・・・"Exp. Anim.. 50. 33-39 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno, K. et al.: "Inhibitory effect of apple pectin and culture condensate of Bifidobacterium longum on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype c-Ha-ras genes"Exp. Anim.. 49. 305-307 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno, K. et al.: "Effect of bacterial metabolism in the intestine on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype c-Ha-ras genes"J. Exp. Clin. Cancer Res.. 20. 51-56 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Birumachi, J. et al.: "Diesel exhaust-induced air way hyperresponsiveness in c-Ha-ras transgenic mice"Toxicol. 163. 145-152 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Umemura, T. et al.: "Buthylhydrixy to luene (BHT) increases susceptibility of transgenic rasH2 mice to lung carcinogenesis"J. Cancer Res. Clin. Oncol.. 127. 583-590 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Maruyama, C., et al.: "Overexpression of human H-ras transgene is responsible for tumors induced by chemical carcinogens in mice"Oncol. Reports. 8. 233-237 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohnishi, Y. et al.: "Induction of drug metabolism-related enzymes by methylcholanthrene and phenobarbital in transgenic mice carrying human prototype c-Ha-ras gene and their wild type littermates"Exp. Anim.. 50(1). 33-39 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narushima, S. et al.: "Effect of intestinal bacteria and functional foods on incidence of colorectal tumors induced by 1,2-dimethylhydrazine (DMH) injection in transgenic(TG) mice harboring human orototype c-Ha-ras genes"Toxicol. Pathol.. 29(suppl.). 260-261 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Maruyama, C., et al.: "Overexpression of human H-ras transgene in tumors of rasH2 mice induced by ethyl-and methyl-nitrosourea"Toxicol. Pathol.. 29(suppl.). 261 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suemizu, H. et al.: "Molecular biological studies in the rasH2 transgenic mouse"Toxicol. Pathol.. 29(suppl.). 263 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai, T. et al.: "Changes in hepatic enzyme activities in transgenic mice carrying human prototype c-Ha-ras gene treated with diethylnitrosamine"J. Vet. Med. Sci.. 64(11). 1065-1067 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suemizu, H. et al.: "Transgene stability and features of rasH2 mice as an animal model for short-term carcinogenicity testing"Molecular Carcinogenesis. 34. 1-9 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohnishi, Y., Arai, T., et al.: "Introduction of drug metabolism-related enzymes by methylcholanthrene and phenobarbital in transgenic mice carrying human prototype c-Ha-ras gene and their wild type littermates"Exp.Anim. 50(1). 33-39 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maruyama, C., Onishi, Y., et al.: "Overexpression of human H-ras transgene is responsible for tumors induced by chemical carcinogens in mice"Oncology Reports. 8. 233-237 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohno, K., Itoh, K., et al.: "Effect of bacterial metabolism in the intestine on colorectal tumors induced by 1, 2-dimethlhydrazine in transgenic mice harboring human phototype c-Ha-ras genes"J.Exp.Clin.Cancer Res. 20. 51-56 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Birumach, J, Hoh, K., et al.: "Diesel exhaust-induced airway hyperresponsiveness in c-Ha-ras transgenic mice"Toxicol. 163. 145-152 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umemura, T., Hioki, K., et al.: "Buthylhydrixy to luene (BHT) increases susceptibility of transgenic rasH2 mice to lung carcinogenesis"J.Cancer Res.Clin.Oncol. 127. 583-590 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Narushima, S., Itoh, K., et al.: "Effect of Intestinal bacteria and functional foods on Incidence of colorectal tumors Induced by 1, 2-dymethylhydrazine (DMH) injection in transgenic mice harboring human prototype c-Ha-ras gene"Toxcol.Pathol. 29(suppl.). 260 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Narushima,S.,Itoh,K. et al.: "Composition of cecal bile acids in ex-germfree mice inoculated with human intestinal bacteria."Lipids. 35・6. 639-644 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohno,K.,Narushima,S.,Itoh,K, et al.: "Inhibitory effect of apple pectin and culture condensate of Bifidobacterium longum on colorectal tumors induced......"Exp.Anim.. 49・4. 305-307 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto,Y.and Itoh,K.: "Bacteroides acidifaciens sp.mov.,isolated from the caecum of mice."Int.J.Syst.Evolu.Microbiol.. 50・1. 145-148 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Marnyama,C.,Ohnishi,Y. et al.: "Over expression of humam H-ras transgenic is responsible for tumors induced by chemical carcinogens in mice."Oncol.Rep.. 8・1. 233-237 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohnishi,Y.,Arai,T. et al.: "Induction of drug metabolism-related enzymes by methylcholanthrene and phenobarbital in transgenic mice......."Exp.Anim.. 50・1. 33-39 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohno,K.,Narashima,S.,Itoh,K. et al.: "Effect of bacterial metabolism in the intestine on colorectal tumors induced by 1,2-dimethylnydrazine in transgenic mice..."J.Exp.Clin.Cancer Res.. 20・1(in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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