The molecular analysis of carcinogenesis in inflamed colon by gpt transgenic mice.
| Project/Area Number |
17590607
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
TAKAHASHI Seiichi Tohoku University, Hospital, Research Associate, 病院, 助手 (40312574)
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| Co-Investigator(Kenkyū-buntansha) |
KINOUCHI Yoshitaka Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (20250780)
NEGORO Kenichi Tohoku University, Hospital, Senior Residents, 病院・医員 (50375028)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | inflammatory bowel disease / carcinogenesis / gpt |
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| Research Abstract |
Individuals with inflammatory bowel disease (IBD) are at increased risk of developing gastrointestinal cancer. Here, we have tested the possibility that chronic inflammation could trigger mutations. For this, we have used IL-10^<+/+>deficient (IL-10^<-/->) mice, which spontaneously develop intestinal inflammation, in combination with a transgenic gpt gene and red gam gene (gpt^+IL-10^<-/->), which is a well-characterized mutation reporter locus. The total mutation frequency in the colon of gpt^+IL-10^<+/+>mice was about five times higher than that in normal gpt^+IL-10^<+/+>mice. In the particular case of G : C to A : T transitions, the frequency of mutations in gpt^+IL-10^<-/-> mice was 4.1 times higher than that in control mice. Interestingly, the frequency of small deletions and insertions was also strikingly increased (10 times). The majority of the deletion or insertion mutations were observed in the monotonous base runs or adjacent repeats of short tandem sequences. In contrast, the frequency of large deletions, detected by loss of the Spi marker present in the red gam transgene, was similar among the mouse strains. Finally, as a control, the mutation frequency in non-inflamed tissues, such as the liver, were similar between gpt^+IL-10^<+/+> mice and gpt^+ IL-10^<+/+> mice. Our data demonstrate that the chronic inflammatory environment in the colon promotes the generation of mutations.
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Report
(3 results)
Research Products
(2 results)
