| Project/Area Number |
12670198
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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 | Gifu University |
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Principal Investigator |
SUGIE Shigeyuki Gifu University, Life Science Research Center, Associate Professor, 生命科学総合実験センター, 助教授 (60187648)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yasuhiro Gifu University, School of Medicine, Department of Pathology, Associate Professor, 医学部, 助手 (70313872)
HARA Akira Gifu University, School of Medicine, Department of Pathology, Associate Professor, 医学部, 助教授 (10242728)
MOEI Hideki Gifu University, School of Medicine, Department of Pathology, Professor, 医学部, 教授 (70021433)
吉見 直己 岐阜大学, 医学部, 助教授 (30166996)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | 1,4-phenylene diisothiocyanate / phenylethyl isothiocyanate / benzylisothiocyanate / Bladder carcinogenesis / hepatocarcinogenesis / Mice / Rats / N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) / 1,4-Phenylene diisothiocyanate / Phenylethylisothiocyanate / イソチオシアネート / 膀胱癌 / N-butyl-N-(4-hydroxybutyl)nitrosamine / ICRマウス / イソチオシアネート系物質 / Diethylnitrosamine(DEN) / 1,4-phenylene diisothiocyanate(DITC) / phenobarbital(PB) / 肝発癌 / glutathione S-transferase placental form(GST-P) |
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| Research Abstract |
1)Modifying effects of 1,4-phenylene diisothiocyanate (DITC) on diethylnitrosamine (DEN)-initiated and phenobarbital (PB)-promoted epatocarcinogenesis were examined in rats. Five weeks old male F344 rats were divided into 8 groups. After a week, Groups 1-5 were given DEN (100mg/kg body weight, i.p.) once a week for 3 weeks, whereas groups 6-8 received vehicle treatment. Group 2 was given 400 ppm DITC containing diet in the initiation phase. From 4 weeks after the start of experiment, groups 3 and 5 were fed DITC, and groups 1-3 and 7 received drinking water containing 500 ppm phenobarbital (PB). Group 6 was given DITC diet alone throughout the experiment (24 weeks). The incidences of hepatocellular adenoma, carcinoma and total liver tumors were significantly smaller in group 2 than those of group 1. The incidence of hepatocellular adenoma was significantly smaller in group 3 than those of group 1. The incidence of hepatocellular adenoma was significantly smaller in group 5 than those o
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f group 4. The average numbers of hepatocellular adenoma, carcinoma and total tumors in group 2 and 3 were significantly smaller than in group 1. The average numbers of hepatocellular carcinoma and total tumors in group 5 were significantly smaller than in group 4. Glutathione S-transferase placental form positive foci were also significantly decreased by DITC treated groups. These results suggest that DITC is a promising chemopreventive agent for liver neoplasia when concurrently administered with PB.
2)The modifying effects of dietary administration of 1,4-phenylene diisothiocyanate (DITC) on N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis during the initiation and post-initiation phases were examined in male ICR mice. Five weeks old animals were divided into 5 groups. Groups 1 to 3 were given OH-BBN (500 ppm) in drinking water for 6 weeks from 6 weeks old. Mice in group 2 were given a diet containing 100 ppm DITC for 8 weeks during the initiation phase, starting from 1 week before OH-BBN exposure. Animals in group 3 were fed the experimental diet for 24 weeks during the post-initiation phase. Mice in group 4 were given only the diet containing the test compound, and those in group 5 were given the basal diet alone throughout the experiment (32 weeks). The frequency of bladder lesions, neoplasms, dysplasia and hyperplasia, was analyzed histopathologically. The cell-proliferation activity estimated by the 5-bromodeoxyuridine labeling index (BrdU-LIs), and cell cycle progression by counting cyclin D1positive cell ratios were compared among the groups using immunohistochemistry. Administration of DITC in the initiation phase significantly reduced the incidence of urinary bladder carcinoma as well as dysplasia, although any lesions of urinary bladder were not decreased in rats treated with DITC in post-initiation phase. Dietary exposure of this agent in initiation phase significantly reduced both BrdU-LIs and cyclin DI positive cell ratios in any bladder lesions. These results suggest that DITC could be a preventive agent against OH-BBN-induced bladder carcinogenesis in mice.
3)The modifying effects of dietary simultaneous or single administration of benzyl isothiocyanate(BITC) and phenylethyl isothiocyanate (PEITC) on M-butyl-AA-(4-hydroxybutyl) nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis during the initiation and post-initiation phases were examined in male F344 rats. Five weeks old animals were divided in to 20 groups. Groups 1 to 13 were given OH-BBN (500 ppm) in drinking water for 8 weeks from 6 weeks old. Rats in groups 2 7 were given a diet containing 0.1 or 0.01% PEITC and/or BITC for 10 weeks during the initiation phase, starting from 1 week before OH-BBN exposure. Animals in groups 8 13 were fed the experimental diet for 26 weeks during the post-initiation phase. Rats in group 14 19 were given only the experimental diets, and those in groups 1 and 20 were given the basal diet alone throughout the experiment (36 weeks). The frequency of bladder lesions, neoplasms1 dysplasia and hyperplasia, was analyzed histopathologically. Single administration of 0.1% PEITC or BITC in postinitiation phase was promoted the size of bladder tumors. Administration of 0.1% PEITC or 0.1% and 0.01% PEITC and BITC in the initiation phase and 0.1% and 0.01% PEITC and BITC in the postinitiation phase significantly reduced the incidence of urinary bladder carcinoma as well as dysplasia. Any tumors could not be found in rats without treatment of OH-BBN. These results suggest that simultaneous administration of BITC and PEITC could deny either promoting effects and be preventive against OH-BBN-induced bladder carcinogenesis in rats. Less
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