Lithocholic acid, a putative tumor promoter, inhibits mammalian DNA polymerase β

Akio Ogawa, Takashi Murate, Motoshi Suzuki, Yuji Nimura, Shonen Yoshida

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Lithocholic acid (LCA), one of the major components in secondary bile acids, promotes carcinogenesis in rat colon epithelial cells induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which methylates DNA. Base-excision repair of DNA lesions caused by the DNA methylating agents requires DNA polymerase β (pol β). In the present study, we examined 17 kinds of bile acids with respect to inhibition of mammalian DNA polymerases in vitro. Among them, only LCA and its derivatives inhibited DNA polymerases, while other bile acids were not inhibitory. Among eukaryotic DNA polymerases α, β, δ, ε, and γ, pol β was the most sensitive to inhibition by LCA. The inhibition mode of pol β was non-competitive with respect to the DNA template-primer and was competitive with the substrate, dTTP, with the Ki value of 10 μM. Chemical structures at the C-7 and C-12 positions in the sterol skeleton are important for the inhibitory activity of LCA. This inhibition could contribute to the tumor-promoting activity of LCA.

Original languageEnglish
Pages (from-to)1154-1159
Number of pages6
JournalJapanese Journal of Cancer Research
Volume89
Issue number11
DOIs
Publication statusPublished - 01-01-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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