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Genetic Alterations Involved in Mouse Colon Tumorgenesis : Comparison between DMH-induced tumors and Spontaneous Tumors

Research Project

Project/Area Number 06670248
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionThe Tokyo Metropolitan Institute of Medical Science

Principal Investigator

OKAMOTO Mieko  The Tokyo Metropolitan Institute of Medical Science. Department of Laboratory Animal Science, Researcher, 実験動物研究部門, 研究員 (80152354)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsmouse colon tumor / dimethylhydrazine / Multiple intestinal neoplasia (Min) / p53 gene / APC gene / ras genes / microsatellite instability / PCR-SSLP / APC遺伝子 / p53遺伝子 / K-、H-、N-ras遺伝子 / Min変異 / 対立遺伝子欠失
Research Abstract

Genetic alterations in spontaneous tumors arising in F1 hybrid mice carring a Min mutation (nonsense mutation in the mouse APC gene) were compared with those in DMH-induced colon tumors developed in F1 hybrids without Min mutation. Tumors in Min mice were developed mainly in the small intestine, and less frequently in the colon.
PCR-SSCP analysis revealed that the vast maiority of the tumors in Min mice had lost their wild-type allele of the APC gene. PCR-SSLP nalysis with markers linked to the APC locus, suggested that allele loss at the APC locus seemed to be inferquent in DMH-induced tumors. Point mutations within the gene were detected in these tumors.
In contrast to the APC gene, neither LOH nor point mutations of the p53 gene were observed in spontaneous tumors in Min mice. DMH-induced tumors showed point mutations and LOH in the p53 gene, although their frequencies being much lower than those in human colon cancers. These data strongly suggest that p53 inactivation is not esential in mouse colon tumorgenesis. Tumors in Min mice showed no point mutations in the K-, H-, and N-ras genes.
PCR-SSLP analyzes with randomly selected markers revealed that microsatellite instability (RER) had frequently occurred in DMH-induced tumors. In contrast, no such instability were detected in spontaneous tumors in Min mice.
All these data indicate that genes involved in colon tumorgenesis may be somewhat different between spontaneous tumors and induced tumors, and also between human FAP (familial adenomatous poliposis) and its mouse model.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Mieko Okamoto: "Mutational and LOH analyses of p53 alleles in colon tumors induced by 1,2-dimethylhydrazaine in F1 hybrid mice." Carcinogenesis. 16. 2659-2666 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 岡本美恵子: "大腸腫瘍発生に関与する遺伝子異常-ヒトとマウスの比較-" 放射線生物研究. 30. 142-156 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 岡本美恵子: "PCR-DNAシーケンス法 In:臨床DNA診断法" 金原出版, 1134 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mieko Okamoto: "Mutational and LOH analysis of p53 alleles in colon tumors induced by 1,2-dimethylhydrazine in F1 hybrid mice" Carcinogenesis. 16 (12). 2659-2666 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mieko Okamoto: "Genetic alterations involved in colon tumorgenesis : comparison between humans and mice" Radiation Biology ResearchCommunications. 30 (3). 142-156 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mieko Okamoto: "PCR-DNA sequencing method (In : Rinsho DNA sindanhou)" Kanehara Shuppan. (in Japanese). 122-130 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okamoto, M.: "Mutational and LOH analyses of p53 alleles in colon tumors induced by 1,2-dimethylhydrazine in F1 hybrid mice." Carcinogenesis. 16. 2659-2666 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡本美恵子: "大腸腫瘍発生に関与する遺伝子異常 -ヒトとマウスの比較-" 放射線生物研究. 30. 142-156 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡本美恵子: "PCR-DNAシーケンス法 In:臨床DNA診断法" 金原出版 古庄敏行,井村裕夫 監修・編集, 1134 (1994)

    • Related Report
      1995 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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