Open AccessLithocholic Acid, a Putative Tumor Promoter, Inhibits Mammalian DNA Polymerase β
Author(s) -
Ogawa Akio,
Murate Takashi,
Suzuki Motoshi,
Nimura Yuji,
Yoshida Shonen
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00510.x
Subject(s) - lithocholic acid , dna , polymerase , biology , microbiology and biotechnology , chemistry , biochemistry , bile acid
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, η, 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 μ M . 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.