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

Jpn J Cancer Res. 1998 Nov;89(11):1154-9. doi: 10.1111/j.1349-7006.1998.tb00510.x.


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 beta (pol beta). 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 alpha, beta, delta, epsilon, and gamma, pol beta was the most sensitive to inhibition by LCA. The inhibition mode of pol beta was non-competitive with respect to the DNA template-primer and was competitive with the substrate, dTTP, with the Ki value of 10 microM. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / pharmacology
  • Carcinogens / toxicity*
  • Colon / drug effects*
  • Colon / enzymology
  • Colon / pathology
  • DNA Polymerase beta / antagonists & inhibitors*
  • Epithelial Cells / drug effects
  • Hydroxylation
  • Isoenzymes / antagonists & inhibitors
  • Kinetics
  • Linear Models
  • Lithocholic Acid / toxicity*
  • Rats


  • Bile Acids and Salts
  • Carcinogens
  • Isoenzymes
  • Lithocholic Acid
  • DNA Polymerase beta