Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase

Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11456-61. doi: 10.1073/pnas.191086798.


Oxygen radicals, which can be produced through normal cellular metabolism, are thought to play an important role in mutagenesis and tumorigenesis. Among various classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is most important because of its abundance and mutagenicity. The MTH1 gene encodes an enzyme that hydrolyzes 8-oxo-dGTP to monophosphate in the nucleotide pool, thereby preventing occurrence of transversion mutations. By means of gene targeting, we have established MTH1 gene-knockout cell lines and mice. When examined 18 months after birth, a greater number of tumors were formed in the lungs, livers, and stomachs of MTH1-deficient mice, as compared with wild-type mice. The MTH1-deficient mouse will provide a useful model for investigating the role of the MTH1 protein in normal conditions and under oxidative stress.

MeSH terms

  • Adenocarcinoma / genetics
  • Alleles
  • Animals
  • Blastocyst
  • Blotting, Western
  • Chimera
  • Clone Cells
  • Crosses, Genetic
  • DNA Damage
  • DNA Primers
  • DNA Repair Enzymes*
  • Exons
  • Female
  • Liver / enzymology
  • Lung Neoplasms / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphoric Monoester Hydrolases / genetics*
  • Recombination, Genetic
  • Restriction Mapping
  • Stomach Neoplasms / genetics


  • DNA Primers
  • Phosphoric Monoester Hydrolases
  • 8-oxodGTPase
  • DNA Repair Enzymes