1997 Fiscal Year Final Research Report Summary
Bile acid load on the occurrence process of cholangiocarcinoma, changes in DNA content and expression of oncogene-relating protein
| Project/Area Number |
07671434
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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 |
Digestive surgery
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
KINAMI Yoshio Kanazawa Medical University, Medical Research Institute, Professor, 総合医学研究所, 教授 (00019928)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKOSHI Minoru Medical Research Institute, Assistant, 総合医学研究所, 助手 (90200146)
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| Project Period (FY) |
1995 – 1997
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| Keywords | CHOLANGIOCARCINOMA / OCCURRENCE PROCESS / DNA CONTENT / NUCLEAR AREA / PCNA / P^<53> / BILE ACID LOAD / DIPN |
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| Research Abstract |
(1) Syrian golden hamsters received 500mg/kg body weight of diisopropanolnitrosamine (DIPN) as a carcinogen for 10 weeks, and simultaneously, were given a standard (control) pellet diet, 0.5% taurocholic acid (TCA) or deoxycholic acid (DCA) pellet diet.
(2) The proliferation of bile ductules and cystic bile ductules occurred in the liver of each group at 15-25 weeks. Cholangiocarcinoma was observed in the TCA or DCA group after 15 weeks and the control group after 20 weeks. In all cases, the bile acid groups indicated high occurrence rates of these lesions.
(3) In bile ductule lesions and carcinomas of each group, an increase of nuclear DNA contents and the dispersion of cell population on the DNA histogram were investigated in course of weeks, but those seen in the bile acid groups were remarkable. Besides, heterogeneity of the DNA distribution pattern and DNA polyproidization were observed within respective lesions of not only carcinoma but also bile ductules.
(4) The nuclear area in all lesions of each group increased with course of weeks, but there were significant differences in bile ductule lesions between the bile acid groups and control group (p<0.05,0.01). Positive cell rates of proliferating cell nuclear antigen (PCNA) also were similar to the findings of nuclear area. The bile acid groups revealed high PCNA positive cell rates in respective lesions.
(5) Expression of mutant P^<53> protein in bile ductule lesions examined by immunohistochemical staining were low in all groups, but the DCA group indicated a high rate of 37% at 25 weeks. Regarding P^<53> positive rates in carcinomas, the DCA group revealed also a high rate of 50%.
(6) The results suggest that bile acid load promotes the proliferation and malignant alteration of DIPN-induced bile ductules and carcinoma, and that a bile ductule-carcinoma sequence may be present in the development of cholangiocarcinoma.
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