1998 Fiscal Year Final Research Report Summary
Role of genotoxic stress-induced apoptosis in the protective effect of dietary fiber against tumorigenesis in the large bowel
| Project/Area Number |
09660123
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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 |
食品科学・栄養科学
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KASAI Takanori Fac.of Agr., Hokkaido Univ.Pro., 農学部, 教授 (80001444)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZUKA Satoshi Fac.of Agr., Hokkaido Univ.Inst., 農学部, 助手 (00271627)
SONOYAMA Kei Fac.of Agr., Hokkaido Univ.Inst., 農学部, 助手 (90241364)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Dietary fiber / Colon cancer / Apoptosis / p53 / Activin / p21 / Bax |
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| Research Abstract |
The present study investigated the role of genotoxic stress-induced apoptosis in the protective effect of dietary fiber against tumorigenesis in the large bowel. Dietary beet fiber increased the apoptotic frequency in rat colonic epithelium at 6 h after a subcutaneous injection of carcinogen 1 , 2-dimethylhydrazine (DM11). The finding suggests that increased efficiency of elimination of damaged cells may be associated with the anti-tumorigenic effect of dietary beet fiber. Semi-quantitative RT-PCR demonstrated that increase in the expression of cyclin-dependent kinase inhibitor p21 and apoptosis inducer Bax genes, which are targets of tumor suppressor protein p53, preceded the apoptosis in rat colonic epithelium following DMH injection. In addition, gene expression of betaA-subunit of activin which is a member of TGF43 gene superfamily was also shown to be upregulated, To establish in vitro model for the investigation of these phenomena at cellular and molecular bases, we examined the time-course of changes in cell mortality and gene expression following different doses of UV irradiation in the untransformed cell line IEC-6 which was derived from rat small intestine. Cell survival rates were decreased by UV irradiation in time- and energy-dependent fashion. Agarose gel electrophoresis of cellular DNA demonstrated that the cell death was due to apoptosis. Semi-quantitative RT-PCR revealed the increase in mRNA levels of betaA-subunit of activin in IEC-6 cells following UV irradiation, being similar to that in rat colonic epithelium following DM14 treatment. The next step concerns whether the dietary fiber and its fermentation products short chain fatty acids modulate the cell cycle, apoptosis, and expression of related genes the colonic epithelial cells following genotoxic agents.
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