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

Abstract

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.

• Authors: T Tsuzuki, A Egashira, H Igarashi, T Iwakuma, Y Nakatsuru, Y Tominaga, H Kawate, K Nakao, K Nakamura, F Ide, S Kura, Y Nakabeppu, M Katsuki, T Ishikawa, M Sekiguchi
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 98 Issue 20 Pg. 11456-61 (Sep 25 2001) ISSN: 0027-8424 [Print] United States
• PMID: 11572992 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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)