| Project/Area Number |
11671586
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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 |
Urology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
KONDO Yukihiro Nippon Medical School, Dept. of Urology, Associate Professor, 医学部, 助教授 (80215467)
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| Co-Investigator(Kenkyū-buntansha) |
AKIMOTO Masao Nippon Medical School, Dept. of Urology, Professor, 医学部, 教授 (50089752)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | bladder cancer / metallothionein / carcinogenesis / tumor progression / 増殖因子 / 亜鉛 / BBN |
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| Research Abstract |
(1) Immortalized metallothionein null cells
Immortalized metallothionein(MT) null cells were established by transfection of simian virus 40 into MT null fibroblast. Additionally, immortalized control fibroblast were established. Immortalized MT null cells showed increased sensitivity cadmium not to zinc, copper, mercury or nickel. These results were written in Life Science, 64,1999,145-150.
(2) Metallothionein prevents the carcinogenicity.
We examined the carcinogenicity of N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) in transgenic mice deficient in the MT I and II genes and control (129/Sv) mice. BBN induced bladder tumors in 75% of MT null mice and in 43% of 129/Sv mice. The average number of bladder tumors per mouse was significantly higher in MT null mice than in 129/Sv mice. Zinc treatment suppressed the carcinogenicity of BBN in 129/Sv mice but not in MT null mice. These results were written in Carcinogenesis, 20, 1999, 1625-1627.
(3) Histopathologic examination
Histopathologic examination revealed that all tumor samples showed morphological changes characteristic of transitional cell carcinoma in both MT null and 129/Sv mice. The major bladder tumors in 129/Sv mice displayed the features of high grade, whereas none of the tumors in MT null mice were designated as grade III.Thus, the malignant potential of bladder tumors in 129/Sv mice was greater than that in MT null mice.
(4) MT null bladder tumor cell line
We established MT null and 129/Sv bladder tumor cell line. MT null bladder tumor cells were unable to induced MT by administered cadmium. These cells were sensitive to cadmium and cisplatin against 129/Sv bladder tumor cells.
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