2010 Fiscal Year Final Research Report
Histopathological study of Barrett's adenocarcinoma using analyses of mitochondrial DNA mutations
| Project/Area Number |
21790385
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
MUKAISHO Kenichi Shiga University of Medical Science, 医学部, 助教 (50343223)
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| Project Period (FY) |
2009 – 2010
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| Keywords | Barrett食道 / ミトコンドリアDNA / ラット逆流モデル / 突然変異解析 |
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| Research Abstract |
To elucidate the histogenesis of Barrett's esophagus (BE) progressing to esophageal adenocarcinoma (EAC), we examined mitochondrial DNA mutations and performed immunohistochemical staining and enzyme histochemistry of cytochrome c oxidase in various lesions (BE, EAC, squamous dysplasia, and squamous cell carcinoma). These lesions were induced in rat duodenal contents reflux models, which were previously reported models that had undergone esophagojejunostomy without gastrectomy. Previously, we reported that high dietary animal fat alters bile acid composition by increasing the concentration of taurine conjugates in bile. These increased bile acids promote the development of BE and Barrett's dysplasia progressing to EAC. In the present study, the reflux animal models were divided into two groups on the basis of their diet. The standard diet group was fed with a low soybean oil diet (CE-2) and the high-fat group was fed with a high cow fat diet (Quick Fat). The animals that survived the operation were sacrificed at postoperative weeks 10, 20, and 30. Cytochrome c oxidase was analyzed in the resected esophagi by both immunohistochemical staining and enzyme histochemistry. Cytochrome c oxidase-negative foci were detected in cases that demonstrated mitochondrial mutations, and these foci increased in a time-dependent manner. A significantly higher number of foci were observed in the high-fat group compared with the standard diet group. We observed that cytochrome c oxidase-negative foci first appeared in the proliferative zone of BE with goblet cells, and then proliferated in a manner similar to crypt fission of intestine. These foci were also detected in the normal regenerative squamous epithelium. However, we could not demonstrate the relationship between BE carcinogenesis and mitochondrial mutations.
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