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

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

研究成果: Article査読

99 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1154-1159
ページ数6
ジャーナルJapanese Journal of Cancer Research
89
11
DOI
出版ステータスPublished - 1998
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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