Suppression of intestinal neoplasia by DNA hypomethylation

Cell. 1995 Apr 21;81(2):197-205. doi: 10.1016/0092-8674(95)90329-1.


We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on ApcMin-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-aza-deoxycytidine, reduced the average number of intestinal adenomas from 113 in the control mice to only 2 polyps in the treated heterozygotes. Hence, DNA methyltransferase activity contributes substantially to tumor development in this mouse model of intestinal neoplasia. Our results argue against an oncogenic effect of DNA hypomethylation. Moreover, they are consistent with a role for DNA methyltransferase in the generation of the C to T transitions seen at high frequency in human colorectal tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / enzymology
  • Adenomatous Polyposis Coli / etiology
  • Adenomatous Polyposis Coli / genetics*
  • Animals
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • DNA Modification Methylases / antagonists & inhibitors
  • DNA Modification Methylases / metabolism*
  • Decitabine
  • Heterozygote
  • Intestinal Polyps / enzymology
  • Intestinal Polyps / etiology
  • Intestinal Polyps / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Biological
  • Suppression, Genetic*
  • Time Factors


  • Decitabine
  • DNA Modification Methylases
  • Azacitidine