Reference SummaryTao L, Toxicology 2004 Mar 1;196(1-2):127-36

Title

 Hypomethylation of DNA and the insulin-like growth factor-II gene in dichloroacetic and trichloroacetic acid-promoted mouse liver tumors.

Authors

 Tao L; Li Y; Kramer PM; Wang W; Pereira MA

Journal

 Toxicology

Volume

 196

Issue

 1-2

Year

 2004

Pages

 127-36

Abstract

 Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver carcinogens. DNA hypomethylation is a common molecular event in cancer that is induced by DCA and TCA. Hypomethylation of DNA and the insulin-like growth factor-II (IGF-II) gene was determined in DCA- and TCA-promoted liver tumors. Mouse liver tumors were initiated by N-methyl-N-nitrosourea and promoted by either DCA or TCA. By dot-blot analysis using an antibody for 5-methylcytosine, the DNA in DCA- and TCA-promoted tumors was demonstrated to be hypomethylated. The methylation status of 28 CpG sites in the differentially methylated region-2 (DMR-2) of mouse IGF-II gene was determined. In liver, 79.3 +/- 1.7% of the sites were methylated, while in DCA- and TCA-treated mice, only 46.4 +/- 2.1% and 58.0 +/- 1.7% of them were methylated and 8.7 +/- 2.6% and 10.7 +/- 7.4% were methylated in tumors. The decreased methylation found in liver from mice exposed to DCA or TCA occurred only in the upstream region of DMR-2, while in tumors it occurred throughout the probed region. mRNA expression of the IGF-II gene was increased in DCA- and TCA-promoted liver tumors but not in non-involved liver from DCA- and TCA-exposed mice. The results support the hypothesis that DNA hypomethylation is involved in the mechanism for the tumorigenicity of DCA and TCA.

Links

 J:90225 – MGI References
15036762 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(C57BL/6 x C3H)F1 Liver tumor Liver

0
(C57BL/6 x C3H)F1 Liver tumor
  • N-methyl-N-nitrosourea (MNU)
 Liver

0
(C57BL/6 x C3H)F1 Liver tumor
  • N-methyl-N-nitrosourea (MNU)
  • dichloroacetic acid
 Liver

observed
(C57BL/6 x C3H)F1 Liver tumor
  • N-methyl-N-nitrosourea (MNU)
  • trichloroacetic acid
 Liver

observed
(C57BL/6 x C3H)F1 Liver tumor
  • dichloroacetic acid
 Liver

0
(C57BL/6 x C3H)F1 Liver tumor
  • trichloroacetic acid
 Liver

0