• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

promoting mechanism of lithocholic acid in colon carcinogenesis induced by monomethylating agents

Research Project

Project/Area Number 10671173
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionNagoya University

Principal Investigator

KAMIYA Junichi  Nagoya University, School of Medicine, Assistant Professor, 医学部, 講師 (70194975)

Co-Investigator(Kenkyū-buntansha) YUASA Norihiro  School of Medicine, Research Associate, 医学部, 助手 (00303610)
NAGINO Masato  School of Medicine, Assistant Professor, 医学部, 講師 (20237564)
NIMURA Yuji  School of Medicine, Professor, 医学部, 教授 (80126888)
Project Period (FY) 1998 – 1999
KeywordsLithocholic acid / DNA polymerase / Tumor promoter / Colon carcinogenesis / bile acids / alkylating agents / Inhibition / Base-excision repair
Research Abstract

1. Seventeen kinds of bile acids were examined with respect to inhibition of enkaryotic DNA polymerase (pol) α, β, γ, δ, and ε in vitro. Only lithocolic acid (LCA) and its derivatives inhibited by LCA. The inhibition mode of pol β was the most sensitive to inhibition by LCA. The inhibition mode of pol β was non-competitive with DNA template-primer and was competitive with substrate with the Ki value of 10 μM. Chemical structures of C-7 and C-12 positions in the sterol skeleton were important for the inhibitory activity of LCA. With respect to inhibition of DNA replicative polymerases, LCA mildly inhibited pol α, while it did not inhibited pol δ. LCA weakly inhibited pol ε, that plays a role in the UV-induced nucleotide excision repair and DNA replication. LCA weakly inhibited pol γ, a mitchondrial DNA replicative polymerase.
2. In a human leukemic cell line (K562), to examine the effect of bile acids on cytotoxicities caused by DNA monomethylating agents or UV irradiation, bile acids were added after the treatment with methyl methanesulfonate or UV irradiation. LCA mildly enhanced cytotoxic effect of methyl methanesulfonate without promoting cytotoxity to pol β and the weak inhibition to pol ε of LCA in vitro.
LCA may suppress base-excision repair that is dependent on pol β, a repair pathway of DNA damages caused by monomethylating agents, via the pol β inhibition. The inhibition of base-excision repair by LCA could be correlated with its tumor promoting activity in colon cancer induced by alkylating agents.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Takeuchi E: "Ligation of portal vein branch induces DNA polymerases α, δ, and εin nonligated lobes"Surg Res. 65. 15-24 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi E: "Research review : DNA polymerases as molecular markers of the regenerating capacity of hepatocytes"J. Hep Bil Pancr Surg. 4. 254-262 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa A.: "Sulfated glycoglycerolipid from archaebacterium inhibits eukaryotic DNA polymerasea α, β and retroviral reverse transcriptase and affects the methyl methanesulfonate cytotoxicity"Int. J. Cancer. 76. 512-518 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa A.: "Lithocholic acid, a putative tumor promoter, inhibits mammalian DNA polymeraseβ"Jpn. J. Cancer Res.. 89. 1154-1159 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi E: "Ligation of portal vein branch induces DNA polymerases a, d, and e in nonligated lobes."Surg Res. 65. 15-24 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi E: "Research review : DNA polymerases as molecular markers of the regenerating capacity of hepatocytes"J. Hep Bil Pancr Surg. 4. 254-562 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa A: "Sulfated glycolycerolipid from archaebacterium inhibits eukaryotic DNA polymerasea a, b and retroviral reverse transcriptase and affects the methyl methanesulfonate cytotoxicity"INt. J. Cancer. 76. 512-518 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa A: "Lithocholic acid, a putative tumor promoter, inhibits mammalian DNAnpolymerase b"Jpn. J. Cancer Res. 89. 1154-1159 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi