| Project/Area Number |
08670270
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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 |
Experimental pathology
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
TATEMATSU Masae Aichi Cancer Center Research Institute, Department of Pathology, Chief, 病理学第一部, 部長 (70117836)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Hayao Aichi Cancer Center Research Institute, Department of Pathology, Section Head, 病理学第一部, 室長 (20207830)
INADA Ken-ichi Aichi Cancer Center Research Institute, Department of Pathology, Senior Research, 病理学第一部, 主任研究員 (70246081)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | 1,2-dimethylhydrazine (DMH) / chimeric mouse / rat / aberrant crypt foci (ACF) / C3H specific antigen (CSA) / crypt isolation / colon carcinogenesis / monoclonal growth / 1,2-dimethylhydrazine(DMH) / Abevvant Ciypt Foci(ACF) / C3H系統特異抗体(CSA) / Aberrant crypt foci(ACF) / C3H系統特異抗体 |
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| Research Abstract |
1. Development of normal colonic crypts and DMH-induced ACF in rats : it was shown that normal postnatal rat colonic crypts reproduced themselves by fission mechanism and as was also the case with DMH-induced ACF.
2. Distribution of PhlP-induced rat ACF : Intragastrical administration of PhlP induced rat ACF mainly in the distal colon at weeks 12 and 25 and predominanly in the proximal colon at week 50 after the treatment. The number of ACF decreased in the distal colon and increased in the proximal colon with time. Cancers were mostly localized in the proximal colon at week 50. It suggested that the early distal ACF were reversible and some of late distal ACF might have developed into cancers.
3. Colonic crypts isolation and clonal analysis with C3H-specific monoclonal antibody (CSA) in chimeric mice : Normal single colonic crypt of chimeric mice were revealed as clonal and the mucosa showed like a patchwork consisting of two groups of crypts derived from the same clonal origin. As far as we investigated, all crypts were constituted with eighter orgin of a strain in a DMH-induced ACF in chimeric mice.
4. Clonal analysis of colonic crypts in chimeric mice by microsatellite polymorphism : Using PCR reaction, a DNA microsatellite marker D8Mit4, polymorphic among strains, could distinguish the clonal origin of isolated crypts of chimeric mice. The result was identical with that judged by CSA staining.
5. Conclusion : With the above results, we hypothesized that ACF were monoclonally developed from a single colonic crypt by fission mechanism. The results of CSA staining proved this hypothesis to be true. Investigation of ACF in terms of distribution, morphology, genetic change, and clonality may reveal the character of reverlibility and irreversiblity of ACF as a precancerous lesion of colonic tumor.
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