Spontaneous Mutations in Digestive Tract of Old Mice Show Tissue-Specific Patterns of Genomic Instability
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- Tetsuya Ono
- 1Genome and Radiation Biology and Divisions of
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- Hironobu Ikehata
- 1Genome and Radiation Biology and Divisions of
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- Vishnu Priya Pithani
- 1Genome and Radiation Biology and Divisions of
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- Yoshihiko Uehara
- 1Genome and Radiation Biology and Divisions of
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- Yali Chen
- 1Genome and Radiation Biology and Divisions of
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- Yoshitaka Kinouchi
- 2Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan; and
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- Toru Shimosegawa
- 2Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan; and
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- Yoshio Hosoi
- 3Department of Radiation Research, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
書誌事項
- 公開日
- 2004-10-01
- DOI
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- 10.1158/0008-5472.can-04-1476
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>In an attempt to evaluate the possible role of mutations in the age-dependent increase of tumor incidence, we studied the mutational burden that accumulates in the aging process in different parts of the digestive tract in mice. The mutations were monitored in lacZ genes integrated in the mouse genome. The digestive tract was divided into the esophagus, stomach, proximal, medial, and distal part of the small intestine, and the colon. Epithelial tissues were separated from these tissues with the exception of the esophagus, in which case the whole tissue was examined. At a young age, the mutant frequencies as well as the molecular nature of the mutations were similar among the tissues examined. In old age, on the other hand, mutant frequencies were elevated to different degrees among the tissues; they were high in the small intestine and colon, intermediate in the stomach, and low in the esophagus. The molecular characteristics of the mutations also revealed distinct tissue-specificity; there were elevated rates of a small deletion mutation in the esophagus, G:C to T:A transversion in the proximal small intestine, and multiple mutations in the distal small intestine and colon. The results indicate that different parts of the digestive tract suffer from different kinds of mutational stress in the aging process. The nature of the multiple mutations suggests the presence of a mutator phenotype based on an imbalance in deoxyribonucleotide pools.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 64 (19), 6919-6923, 2004-10-01
American Association for Cancer Research (AACR)
