General sessions1D-06 The roles of tumor-associated genes, Mutyh, Msh2 and Trp53, in the suppression of oxidative stress-induced tumorigenesis in mice

• Published in: Genes & Genetic Systems Vol. 84; no. 6; p. 461
• Main Authors: NAKATSU Yoshimichi, MATSUMOTO Noritaka, PIAO Jingshu, TSUZUKI Teruhisa
• Format: Journal Article
• Language: Japanese
• Published: The Genetics Society of Japan 2009
• ISSN: 1341-7568; 1880-5779

8-Oxoguanine is a highly mutagenic DNA lesion induced by oxidation within normally growing cells. Three enzymes, MTH1, OGG1, and MUTYH play important roles in avoiding the 8-oxoG-related mutagenesis in mammal. We have established an experimental system for oxidative stress-induced tumorigenesis in the intestines of mice. Oral administration of KBrO3 effectively induced epithelial tumors in the small intestines of Mutyh- or Msh2-deficient mice, indicating the significance of Mutyh and Msh2 in the suppression of tumorigenesis induced by oxidative stress. To examine the roles of tumor-suppressor Trp53 gene in the suppression of oxidative stress-induced tumorigenesis, we performed KBrO3-induced tumorigenesis experiments using Trp53-deficient mice. We observed an enhanced tumor-formation in the small intestines of Trp53-deficient mice, as compared to the treated wild-type or untreated mutant mice. These results indicate that Trp53 play roles in the suppression of tumorigenesis induced by oxidative stress. We will discuss the roles of Mutyh, Msh2, and Trp53 in the suppression of oxidative stress-induced mutagenesis and tumorigenesis in mice.