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Cell cycle checkpoint after DNA damage during in vitro hepatocarcinogenesis

Research Project

Project/Area Number 07670229
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionAsahikawa Medical College

Principal Investigator

OGAWA Katsuhiro  Asahikawa Medical College, Pathology, Professor, 医学部, 教授 (50045514)

Co-Investigator(Kenkyū-buntansha) SAITO Yoshinori  Asahikawa Medical College, Pathology, Assistant, 医学部, 助手 (70241429)
LEE Gang-Hong  Asahikawa Medical College, Pathology, Assistant Professor, 医学部, 助教授 (10261405)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Keywordsp53 / UV / H-ras / mouse immortal hepatocytes / H-ras / マウス / 肝細胞 / 染色体不安定化
Research Abstract

Cell cycle checkpoint was investigated after DNA damage in normal, immortal and malignantly-transformed hepatocytes, and following points were clarified.
1. Many immortal hepatocyte clones were isolated from hepatocyte colonies developing during primary cultures of mouse hepatocytes. By introducing the mutationally-activated H-ras gene to these cells, many malignantly-transformed cell lines were also produced. Using these cells as well as primary hepatocyte cultures, it became possible to compare cell cycle checkpoint in normal, immortal and malignant cells carrying the same background.
2. When normal hepatocytes were exposed to DNA damaging agents, cell growth was completely inhibited, and cell cycle was arrested at G1 phase. During this period, half life of p53 was markedly extended, and p53 was overexpressed in the nuclei. Suppression of p53 protein using p53 antisense oligonucleotide resulted in abrogation of G1 arrest.
3. Although normal and immortal cells showed G1 arrest after UV damage, it was much less evident in H-rastransformed cells.
4. There was no p53 mutations in any of malignant cells, and overexpression of p53 occurred after UV damage. These observations indicate that downstream of the p53 pathway may be knockout by H-ras.
5. Malignant cells show much greater variation of chromosomal numbers than immortal cells, suggesting that loss of cell cycle checkpoint can result in chromosomal instability.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Yoshida, Y.: "Intrahepatic transplantation of normal hepatocytes prevents Wilson's disease in Long‐Evans cinnamon rats." Gastroenterology. 11. 1654-1660 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Obata, M.: "Identification of the Part2 (Pulmonary adenoma resistance) locus on mouse chromosome 18, a major genetic determinant for lung carcinogen ersistance in BALB/cByJ mice." Oncogene. 13. 1599-1604 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Obata, M.: "Loss of heterozygosity at loci on chromosome 4, a common genetic event during the spontaneous immortalization of mouse embrvonic fibroblasts." Mol. Carcinogenesis. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Lee, G‐H: "Genetic dessection of susceptibility to murine ovarian teratomas that originate from parthenogenetic oocytes." Chncer Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ogawa, K: "Absence of p53 mutation in methylnitrosoures induced mammary tumors in rats." Cancer Detect. Prevent.20. 214‐217 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishikawa, Y,: "Hepatocytic cells form bile duct‐leke structures within a three‐dimensional collagen gematrix." Exp. Cell Res.223. 357-371 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Obata, M., Kanda, H,Kitagawa, T., Ogawa, K.and Lee, G.H.: "Loss of heterozygosity at loci on chromosome 4, a common genetic event during the spontaneous immortalization of mouse embryonic fibroblasts." Mol.Carcinogenesis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishikawa, Y., Tokusashi, Y., Kadohama, T., Nishimori, H,and Ogawa, K.: "Hepatocytic cells form bile duct-like structures within a three-dimensional collagen gel matrix." Exp.Cell Res.223. 357-371 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saito, Y.and Ogawa, K.: "Wild type p53 and c-myc cooperation generating apoptosis of a rat hepatocellular carcinoma cell line (FAA-HTC1)." Oncogene. 11. 1013-1018 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Lee, G.H., Ogawa, K., Nishimori, H,and Drinkwater, N.R.: "Most liver epithelial cell lines from C3B6F1 mice exhibit parentally-biased loss of heterozygosity at the Lci (Live cell immortalization) locus on chromosome4." Oncogene. 11. 2281-2287 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kadohama, T., Tsuji, K.and Ogawa, K.: "Indistinct cell cycle checkpoint after U.V.damage in H-rass transformed mouse liver cells despite normal p53 gene expression." Oncogene. 9. 2845-2852 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuji, K.and Ogawa, K.: "Recovery from ultraviolet-induced growth arrest of primary rat hepatocytes by p53 antisense oligonucleotide treatment." Mol.Carcinogenesis. 10. 45-51 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishimori, H., Ogawa, K.and Tateno, H.: "Frequent deletion in chromosome 4 and duplication of chromosome 15 in liver epithelial cells derived from long-term culture of C3H mouse hepatocytes." Int.J.Cancer. 59. 108-113 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshida,Y.: "Intrahepatic transplantation of narmal hepatocytes prevents Wilson's disease in Long-Evans cinnamon rats." Gastroenterology. 11. 1654-1660 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Obata,M.: "Identification of the Par2 (Pulmonary adenoma resistance) locus on mouse chromosome 18,a major genetic determinant for lung carcinogen resistance in BALB/cByJ mice." Oncogene. 13. 1599-1604 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Obata,M.: "Loss of heterozygosity at loci on chromosome 4,a common genetic event during the spontaneous immortalization of mouse embryonic fibroblasts." Mol.Carcinogenesis. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Lee,G-H.: "Genetic dissection of susceptibility to murine ovarian teratomas that originate from parthenogenetic oocytes." Cancer Res.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Ogawa,K.: "Absence of p53 mutation in methylnitrosourea-induced mammary tumors in rats." Cancer Detect.Prevent.20. 214-217 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishikawa,Y.: "Hepatocytic cells form bile duct-like structures within a three-dimensional collagen gel matrix" Exp.Cell Res.223. 357-371 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Lee,G-H: "Most liver epithelial cell lines from C3B6F1 mice exhibit parentally-biased loss of heterozygosity at the Lci (liver cell immortalization) locus on chromosome4." Oncogene (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Lee,G-H: "Conditional transformation of mouse liver epithelial cells : an in vitro model for analysis of genetic events in hepatocarcinogenesis." Am.J.Pathol.147. 1811-1822 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saito,Y.: "Wild type p53 and c-myc cooperation in generating apoptosis of a rat hepatocellular carcinoma cell line (FAA-HTCl)." Oncogene. 11. 1013-1018 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ogawa,K.: "Absence of p53 mutations in methylnitrosourea-induced mammary tumors in rats." Cancer Detect.Prevent. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Tokusashi,Y: "Differentiation of the normal and mutant rat albumin genes on hepatic tissue sections by in situ PGR." Nucl.Acids Res.23. 3790-3791 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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