1997 Fiscal Year Final Research Report Summary
Physiological and Clinical Implication of Metallothionein
| Project/Area Number |
08044317
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Biological pharmacy
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
IMURA Nobumasa Kitasato Univ., Pharmaceutical Sci., Professor, 薬学部, 教授 (70012606)
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| Co-Investigator(Kenkyū-buntansha) |
LAZO John.S. Univ.of Pittsburgh, Sch.of Medicine, Professor, 医学部, 教授
KONDO Yukihiro Nippon Medical School, Dept.of Urology, Assistant Professor, 医学部, 講師 (80215467)
NAGANUMA Akira Tohoku Univ., Faculty of Pharmaceutical Sci., Professor, 薬学部, 教授 (80155952)
HIMENO Seiichiro Kitasato Univ., Pharmaceutical Sci., Associate Professor, 薬学部, 助教授 (20181117)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Metallothionein / Knockout mouse / Carcinogenesis / Heavy metal / Anticancer drug / Apoptosis |
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| Research Abstract |
1. To examine the protective role of physiological concentration of metallothionein (MT) against chemical carcinogenesis, MT-I and -II null (MTKO) and control (129/SV) mice were given N-butyl-N-4-hydroxybutyl nitrosamine (BBN) and the formation of bladder tumors were examined. The incidence of bladder tumor in MTKO mice was 72.9%, whereas 42.9% in 129/SV mice. Zn administration reduced the tumor incidence only in 129/SV mice. These data suggested that the baseline level of MT has protective role against chemical carcinogenesis.
2. SV40-transformed fibloblasts were obtained from both MTKO and 129/SV embryonic primary cultured cells. We established cisplatin-resistant and Cd-resistant MT null cells by gradual escalation of chemicals in the medium. Cisplatin-resistant MT null cells showed cross-resistance to Melphalan, paraquat and other ROI inducing agents. The cellular levels of thioredoxin and Ref-1, the latter molecule confers not only the redox regulation in the nucleus but blso the DNA repair by its endonuclease activity, were increased in cisplatin-resistant MT null cells. The accumulation of cisplatin as determined by Pt incorporation into the cells was lower in cisplatin-resistant MT null cells. Cd-resistant MT null cells also showed decreased accumulation of Cd compared to the parental MT null cells. The results of this study enabled further clarification of factors involved in cisplatin or Cd resistance other than MT.
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