MUTYH-null mice are susceptible to spontaneous and oxidative stress-induced intestinal tumorigenesis

Katsumi Sakamoto, Yohei Tominaga, Kazumi Yamauchi, Yoshimichi Nakatsu, Kunihiko Sakumi, Kaoru Yoshiyama, Akinori Egashira, Shinobu Kura, Takashi Yao, Masazumi Tsuneyoshi, Hisaji Maki, Yusaku Nakabeppu, Teruhisa Tsuzuki

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116 Citations (Scopus)


MUTYH is a mammalian DNA glycosylase that initiates base excision repair by excising adenine opposite 8-oxoguanine and 2-hydroxyadenine opposite guanine, thereby preventing G:C to T:A transversion caused by oxidative stress. Recently, biallelic germ-line mutations of MUTYH have been found in patients predisposed to a recessive form of hereditary multiple colorectal adenoma and carcinoma with an increased incidence of G:C to T:A somatic mutations in the APC gene. In the present study, a systematic histologic examination revealed that more spontaneous tumors had developed in MUTYH-null mice (72 of 121; 59.5%) than in the wild type (38 of 109; 34.9%). The increased incidence of intestinal tumors in MUTYH-null mice (11 tumors in 10 of 121 mice) was statistically significant compared with the wild type (no intestinal tumors in 109 mice). Two adenomas and seven adenocarcinomas were observed in the small intestines, and two adenomas but no carcinomas were found in the colons. In MUTYH-null mice treated with KBrO3, the occurrence of small intestinal tumors dramatically increased. The mean number of polyps induced in the small intestines of these mice was 61.88 (males, 72.75; females, 51.00), whereas it was 0.85 (males, 0.50; females, 1.00) in wild-type mice. The tumors developed predominantly in the duodenum and in the upper region of the (jejunum) small intestines. We conclude that MUTYH suppresses spontaneous tumorigenesis in mammals, thus providing experimental evidence for the association between biallelic germ-line MUTYH mutations and a recessive form of human hereditary colorectal adenoma and carcinoma.

Original languageEnglish
Pages (from-to)6599-6604
Number of pages6
JournalCancer Research
Issue number14
Publication statusPublished - Jul 15 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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