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Analyses of clonality and genomic changes in the regeneration of gastric mucosa

Research Project

Project/Area Number 09670248
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

INADA Ken-ichi  Aichi Cancer Center Research Institute, Laboratory of Pathology, Senior Researcher, 病理学第一部, 主任研究員 (70246081)

Co-Investigator(Kenkyū-buntansha) WATANABE Hiromitsu  Department of environment and mutation, Research Institute for Radiation Biology and Medicine, Hiroshima University, Professor, 原爆放射能医学研究所・環境生物研究部門・環境変異研究分野, 教授 (00034653)
TATEMATSU Masae  Aichi Cancer Center Research Institute, Laboratory of Pathology, Chief, 病理学第一部, 部長 (70117836)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsfreeze-ulceration / catechol / crypt-isolation / intestinal metaplasia / mucosal regeneration / chimeric mouse / microsatellite / 凍結潰瘍
Research Abstract

1. We analyzed clonality of regenerative gastric glands in cases of freeze-ulceration, catechol administration, and irradiation. Monoclonality of regenerating glands and a BALB/c-superior strain variation were demonstrated both histologically and genetically, but no sex difference was found.
2.Isolation of regenerative glands by our crypt-isolation technique has not yet been successful because of strong attachment to the stroma and a fragile structure making them susceptible to destruction during isolation process. Radiation- induced intestinal metaplasia in the rat gastric glandular mucosa is frequently- associated with regenerative glands. In order to examine genetic changes, glands were isolated and histologically divided into several subtypes using gastric and intestinal cell differentiation markers. Analyses of changes in p53, K-ras, H-ras, and APC genes are now under way.
3. We have also concentrated attention on the relationship between regeneration and carcinogenic steps in the MNU-initiated chimeric mouse glandular stomach exposed to catechol. Regenerative epithelia, hyperplastic epithelia, adenomas, and carcinomas are all observed in the mucosa in this model. Regenerative and hyperplastic epithelia were demonstrated to be monoclonal at the level of the unit gland in a polyclonal tissue background. Adenomas and the most of carcinomas were monoclonal, but a few large carcinomas proved to be polyclonal probably due to fusion of discrete tumors. Strain differences in carcinogenecity were also preserved in the chimera. With BrdU administration to mice, no proliferative differences were apparent in the normal glandular stomach mucosa. However, lesions growing into the submucosa, frequently observed in hyperplastic epithelium, exhibited a BALB/c-superiority, in this context suggesting strain differences in cellular responses. The interrelationships of the observed lesions are now under investigation.

Report

(3 results)
  • 2000 Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Yamamoto,M. et al.: "Dose-independent induction of both pepsinogen-altered pyloric glands and adenocarcinomas in the glandular stomach of C3H treated with N-methyl-N-nitrosourea"Jpn.J.Cancer Res. 88. 238-244 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masui,T. et al.: "Induction of invasive sauamous cell carcinomas in the forestomach of (c3HXMSM) F1, MSM, and c3H mice by N-methyl-N-nitrosourea and mutational analysts of the H-ras and p53 genes"Cancer Letters. 111. 97-104 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masui,T. et al.: "Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes"Cancer Letters. 112. 33-45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayach,K. et al.: "Effects of carbon tetrachloride administration on initiation of liver cell foci by the non-hepatocarcinegens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo(a)pyrene (B(a)P)"Cancer Letters. 118. 55-60 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi,K, et al.: "Dose-dependent promoting effects of catechol on glandular stomach carcinogenesis in BALB/C mice mitiated with N-methyl-N-nitrosourea"Jpn.J.Cancer Res. 88. 1143-1148 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamachika,T. et al.: "N-methyl-N-nitrosourea concentration-depenclent, rather than total mtake-depenclent, induction of adenocarcinomas in the gladular stomach BALB/C mice"Jpn.J.Cancer Res. 89. 391 (385)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamoto, M.et al.: "Dose-independent induction of both pepsinogen-altered pyloric glands and adenocarcinomas in the glandular stomach of C3H treated with N-methyl-N-nitrosourea"Jpn.J.Cancer Research. 88. 238-244 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masui, T.et al.: "Induction of invasive squamous cell carcinomas in the forestomach of (C3HXMSM)F1, MSM, and C3H mice by N-methyl-N-nitrosourea and mutational analysis of the H-ras and p53 genes"Cancer Letters. 111. 97-104 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masui, T.et al.: "Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes"Cancer Letters. 112. 33-45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi, K.et al.: "Effects of carbon tetrachloride administration on initiation of liver cell foci by the non-hepatocarcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo (a) pyrene (B(a)p)"Cancer Letters. 118. 55-60 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi, K.et al.: "Dose-dependent promoting effects of catechol on glandular stomach carcinogenesis in BALB/c mice initiated with N-methyl-N-nitrosourea"Jpn.J.Cancer Res.. 88. 1143-1148 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamachika, T.et al.: "N-methyl-N-nitrosourea concentration-dependent, rather than total intake-dependent, induction of adenocarcinomas in the glandular stomach of BALB/c mice"Jpn.J.Cancer Res.. 89. 385-391 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamoto M.: "Dose-independent induction of both pepsinogen-altered pyioric grands and adenocarcrnanas in the glandular stomach of c3H treated with N-methy1-N-nrtrosourea" Jpn.J.Cancer Res.88. 238-244 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masui T.: "Induction of invasive squamous cell carcinomas in the forestomach of(C3HyMSM)F1,MSM,and C3H mice by N-methyl-N-nitrosourea and mutational analysis of the H-ras and p53 genes" Cancer Letters. 111. 97-104 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masui T.: "Highly metastatic hepatocellular carcinomas induced in made F344 rats treated with N-nitronsemerpholine in combination with other hepatocarcpnogens shond a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes" Cancer Letters. 112. 33-45 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi K.: "Effects of carbon tetrachloride admmistration on inrtiation of livercell foci by the non-hepatocarcmogens N-methyl-N-nitro-Nenitrosoguanieltne(MMNG)and benzo(a)pyrene(B(a)p)" Cancer Letters. 118. 55-60 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi K.: "Dose-dependent promoting effects of catechd on glandnlar stomach carcinagenesis in BALB/C mice imtiated with N-methyl-N-nitrosourea" Jpn.J.Cancer Res.88. 1143-1148 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamachika T.: "N-methyl-N-nitrosourea concontration-dependent,rather than total intake-dependent,incluction of adenocancinomas in the glandular stomach of BALB/C mice" Jpn.J.Cancer Res.89. 385-391 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ken-ichi,Inada et al.: "Gastric and intestinal mixed and solely intestinal types of intestinl metaplasia in the human stomach" Pathology International. 47. 831-841 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyoshi Kobayashi et al.: "Dose-dependent promoting effects of Catechol on glandular stomach carcinogenesis in BALB/c mice inいtiated with N-methyl-N-nitrosourea" Jpn.J.Cancer Res.88. 1143-48 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 稲田健一 他: "腺管分離法による腸上皮化生腺管の解析 細胞分化と立体構築" 消化器癌の発生と進展. 9. 265-270 (1997)

    • Related Report
      1997 Annual Research Report

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

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