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

98 引用 (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.

元の言語English
ページ(範囲)1154-1159
ページ数6
ジャーナルJapanese Journal of Cancer Research
89
発行部数11
DOI
出版物ステータスPublished - 01-01-1998

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Lithocholic Acid
DNA-Directed DNA Polymerase
Carcinogens
Bile Acids and Salts
DNA
Methylnitronitrosoguanidine
DNA Primers
Sterols
Skeleton
DNA Repair
Colon
Carcinogenesis
Epithelial Cells
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Ogawa, Akio ; Murate, Takashi ; Suzuki, Motoshi ; Nimura, Yuji ; Yoshida, Shonen. / Lithocholic acid, a putative tumor promoter, inhibits mammalian DNA polymerase β. :: Japanese Journal of Cancer Research. 1998 ; 巻 89, 番号 11. pp. 1154-1159.
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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.",
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Lithocholic acid, a putative tumor promoter, inhibits mammalian DNA polymerase β. / Ogawa, Akio; Murate, Takashi; Suzuki, Motoshi; Nimura, Yuji; Yoshida, Shonen.

:: Japanese Journal of Cancer Research, 巻 89, 番号 11, 01.01.1998, p. 1154-1159.

研究成果: Article

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AU - Murate, Takashi

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AU - Nimura, Yuji

AU - Yoshida, Shonen

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N2 - 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.

AB - 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.

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