1992 Fiscal Year Final Research Report Summary
Studies on glutathione S-transferase-pi
| Project/Area Number |
02670327
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Toho University |
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Principal Investigator |
SUGIMOTO Motonobu Toho Uuiv.Sch.of Med., Ass.Prof., 医学部, 助教授 (30120281)
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| Co-Investigator(Kenkyū-buntansha) |
SAIKI Hideki Toho Uuiv.Sch.of Med., Assistant, 医学部, 助手
SATO Takashi Toho Uuiv.Sch.of Med., Assistant, 医学部, 助手
YAMAMURO Wataru Toho Uuiv.Sch.of Med., Assistant, 医学部, 助手 (80166777)
ITO Kinji Toho Uuiv.Sch.of Med., Lecturer, 医学部, 講師 (40057758)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Glutathione S-transferase / Isoenzyme / Precancerous lesion / Primary cultured hepatocytes / Hepatocarcinogenesis / Immunohistochemistry |
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| Research Abstract |
1)The immunohistochemical study was carried out to elucidate the localization of glutathione S-transferase (GST) isozymes in primary liver tumors : 28 lesions of hepatocellular carcinoma (HCC) and 10 cases of cholangiocellular carcinoma (CCC) ; and tumor-like lesions : 2 cases of focal nodular hyperplasia, 5 cases of adenomatous hyperplasia (AH) and 4 cases of licer cell dysplasia. In HCC, GST-alpha positivity was 60%, but GST-pi was negative in all. In CCC. alpha was negative in all, but pi positivity was 80%. In tumor-like lesions, alpha was positive in all, but pi was positive in only 2 cases of AH. pi was suggested to be significant as a marker of CCC. Moreover, since pi was present in some AH, it was suggested that AH might be a precancerous lesion.
2)The changes in GST activity and GST subunit components in primary cultured rat hepatocytes were studied. Enzyme activity decreased at 48hr and subsequently increased and returned by 120hr to levels initially observed at 12hr. lmmunocy
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tochemical study was performed with 3 polyclonal antibodies : anti-Ya, Yb_1 and Yp. With anti-Ya, hepatocytes were persistently positive up to 144hr. With anti-Yb_1, hepatocytes were positive at 24hr, though positivity then gradually decreased. On the other hand, with anti-Yp, cells were almost negative at 48hr and became obviously positive at 96hr. Overall time-dependent increase in the GST activity can be accounted for by increase of Yp subunit.
3) In order to clarify an implication of expression of GST-P (pi-class, Yp-sudunit) in the hepatocarcinogenesis, immunohistochemical study was performed on two rat groups : A-group with continual administration of diethylnitrosamine (DEN) ; B-group with 4 weeks administration of DEN and 8 weeks withdrawal. In A-group, GST-P positive cells were scattered on the 4th day and then minifoci and large foci appeared. From the 6th week hyperplastic nodules with positive GST-P were completed and from the 10th weeks cancer lesions with faint GST-P were recognized. In B-group, GST-P positive large foci changed to minifoci and single cell, and hyperplastic nodules decreased in number disappearing on the 8th week. Precancerous GST-P positive cell was suggested to be reversible. Less
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