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Development of animal model for cancer researches concerning diet and nutrition using rasH2 mice

Research Project

Project/Area Number 09308033
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

MITSUOKA Tomotari  Graduate School of Agriculture and Life Sciences, The University of Tokyo, Honorary Prof., 大学院・農学生命科学研究科, 名誉教授 (30157549)

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)
NOMURA Tatsuji  Central Inst. of Exp. Anim., Head (Researcher), 実験動物中央研究所, 所長(研究職) (10072399)
ITOH Kikuji  Graduate School of Agriculture and Life Sciences, The University of Tokyo, Asosc. Prof., 大学院・農学生命科学研究科, 助教授 (50100045)
NAKAYAMA Hiroyuki  Graduate School of Agriculture and Life Sciences, The University of Tokyo, Associate Prof., 大学院・農学生命科学研究科, 助教授 (40155891)
HIOKI Kyouji  Central Inst. of Exp. Anim., Group Director (Researcher), 実験動物中央研究所, 室長(研究職) (80208735)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 2000: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1999: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1998: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1997: ¥13,200,000 (Direct Cost: ¥13,200,000)
KeywordsCancer / ras mice / transgenic mice / diet / Fermentation products of lactic acid bacteria / 乳酸菌発酵素産物 / アップルペクチン / Bifidobacterium longum
Research Abstract

1. To study the effects of intestinal flora on cancer development, N-methyl-nitrosourea (MNU) and N,N-diethylnitrosoamine (DEN), which induce the mutations in c-Ha-ras genes, were injected to germfree and various types of gnotobiote rasH2 mice. There were no relation between cancer development and the composition of intestinal flora.
2. Although rasH2 mice were inoculated with Aαc, one of heterocyclic amines, and aflatoxin, which are strong carcinogens and ingested from the daily diet, no cancers were observed.
3. Inhibitory effect of various functional foods was studied using rasH2 mice injected with 1,2-dimethylhydrazine (DMH). Apple pectin and culture condensate of Bifidobacterium longum inhibited colorectal tumors. However there were no relation between development of colorectal tumors and the intestinal environments, e.g. composition of intestinal flora, concentrations of organic acids and putrefactive products, composition of bile acids.
4. Culture of Propionibacterium freudereichii, which is used as starter of cheese and is immunomodulator, did not inhibit the colorectal tumors in rasH2 mice induced by DMH. Yogurt, fermented milk by Streptococcus thermophilus and Lactobacillus burgaricus, reduced the incidence of the colorectal tumors in rasH2 mice induced by DMH. Fermented soy bean protein by single culture of Lactobacillus casei, L. fermentum, Saccharomyces cerevisiae or mixed culture of them could inhibited the colorectal tumors, but not fermented protein by Leuconostoc mesenteroides and mixed culture of this with other three strains.
These results indicate that rasH2 mice are good animal model to evaluate the inhibitory effects of functional food on the colorectal tumors.

Report

(5 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Narushima, S.他: "Effect of mouse intestinal bacteria on incidence of colorectal tumors laduced by 1,2-dimethyl-hydnazine injection in gnotopiotic transgenic mice hanboring human prototype c-Ha-ras genes"Exp. Anim.. 47. 111-117 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, S.他: "Validation of thansgenic mice hanboring the human prototype C-Ha-ras gene as a bioassay model for rapid canciaogenicity testing"Toxicol. Lett.. 102-103. 473-478 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno, K.他: "Inhibitory effect of apple pectin and culture condensate of Bifidobacterium longum on colorectal tumors induced by 1,2-dimethylhydnezine in transgenic mice hanboring human"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.他: "Effect of bacterial metabolisan in the intestine on colonectal tumors induced by 1,2-dimethylhydnezine 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(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Birumachi, J.他: "Diesel exhaust-induced airway hypernesponsiveness in c-Ha-ras transgenic 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.他: "Buthylhydrixy to luene (BHT) increases susceptibility of transgenic ras H2 mice to lung cancinogenesis"J. Cancer Res. Clim. 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] Narushima, S. et al.: "Effect of mouse intestinal bacteria on incidence of colorectal tumors induced by 1,2-dimethylhydrazine injection in gnotobiotic transgenic mice harboring human prototype c-Ha-ras genes."Exp. Anim.. 47. 111-117 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, S. et el.: "Varidation of transgenic mice harboring the human prototype c-Ha-ras gene as a bioassay model for rapid carcinogenicity testing"Toxicol. Lett.. 102-103. 473-478 (1998)

    • 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.: "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. 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

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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] 成島聖子,伊藤喜久治: "大腸癌のprevention-食事や腸内細菌叢の変化などを中心に"臨床医. 26・7. 86-88 (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] Maruyama,Co,Nomura,T. et al.: "Over expression of human H-ras transgene is responsible for tumors induced by chemical carcinogens in mice."Oncol.Rep.. 8・1. 233-237 (2001)

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

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

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchida, K., Itoh, K. 他: "Transformation of acids and sterol by clostridia(fujiform bacteria)in wister rats"Lipids. 34(3). 269-273 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Horie, H., Itoh, K. 他: "Effect of intestinal bacteria on the development of colonic neoplasm : an experimental study"European Journal of Center Prevention. 8. 237-245 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Umesaki, Y., Itoh, K. 他: "Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system"Infection and Immunity. 7. 3504-3511 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tamura, M., Itoh, K. 他: "Effect of guar gum and cellulose on cecal enzyme activity and cecal short-chain Fatty acids in young and aged mice."Ann. Nutr. Metab.. 43. 60-65 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyamoto, Y., Itoh, K. 他: "Design of cluster-specific 16SrDNA oligonucleotide probes to identify bacteria of the Bacteroides subgroup harbord in human feces."FEMS Letts.. 177. 143-149 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Narushima,S.,Itoh,K他: "Absence of secondary bile acids in gnotobiotic mice associated with two human in with the ability to dehydroxylate bile acids in vitro."Microbiol.Immunol.. 43(9). 893-897 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 成島聖子,伊藤喜久治: "ノトバイオートマウスにおける腸内フローラ構成と胆汁酸代謝" 腸内細菌学雑誌. 11・2. 89-95 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Narushima,S.,Itoh,K.,他: "Effect of mouse intestinal bacteria on incidance of colureival tumors" Exp.Anim.47・2. 111-117 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tamura,M.,Suzuki,H.他: "Effects of guar gum and fructooligosaccharides on plasma lipids and…" J.Clin.Biochem.Nutr.23・2. 131-137 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Goto,K.,Ohashi,H.他: "Isolation and characterization of hericobacter species from…" Curr.Microbiol.37・1. 44-51 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 成島聖子,伊藤喜久治他: "大腸癌高リスク群と対照群より分離された糞便内Clostuidiumの菌種…" 消化器癌の発生と進展. 10. 459-460 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 堀江久永,岡田真樹 他: "腸内細菌の発癌および腸内環境に与える影響" 消化器癌の発生と進展. 10. 31-32 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tamura,M., Hirayama,K. & Itoh,K: "Comparison of colonic bacterial enzymes in gnotobiotic mice monoassociated with different intestinal pacteria" Microbial Ecology in Health and Disease. 10(6). 287-294 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki,T., Itoh,K., Kaneko,T. & Suzuki,H.: "Inhibition of bacterial translocation from the gastrointestinal tract of mice by oral administration of a cnlture conclensate of Bifidobacterium longum" J.Vet.Med.Sci.59(8). 665-669 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Itoh,K. & Yanabe,M.: "Gnotobiology in laboratory animal production.Germfree Life and its Ramifications." XII ISG Pnblishing Committee,Shiozawa. 13-15 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Narushima,S., Itoh,K., Morita,T., Mitsuoka,T., Nakyata,H., Itoh,T., Hioki,K & Noama,T.: "Effect of in testinal bacteria on incidence of colorectal tumors indnced by 1,2-dimethylhydrazine in jection in transgenic mice carrying human c-Ha-ras genes.Germfree Life and its Ramifications" XII ISG Pnblishing Comittee,Shiozawa. 503-505 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 成島聖子,伊藤喜久治: "ノトバイオートマウスにおける腸内フローラ構成と胆汁酸代謝" 腸内細菌学雑誌. 11. 89-95 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Narushima,S., Itoh,K., Mitsuok,T., Nakyama,H., Itoh,T., Hioki,K. & Nomura,T.: "Effrct of monse lntestinal bacteria on incidence of colorectal tumors indnced by 1,2-dinethylhydrazine indection in gnotobiotic transgenic mice barboring human prototype c-Ha-ras genes" Exp.Animals. 47(2)(in press). (1998)

    • Related Report
      1997 Annual Research Report

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

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