| Project/Area Number |
60440039
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene
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| Research Institution | University of Tokyo |
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Principal Investigator |
WADA Osamu Department of Hygiene & Preventive Medicine, Faculty of Medicine University of Tokyo, 医学部・衛生学教室, 教授 (60009933)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGISAWA Hiroyuki Department of Hygiene & Preventive Medicine, Faculty of Medicine University of T, 医学部・衛生学教室, 助手 (10200536)
NAGAHASHI Masaru Department of Hygiene & Preventive Medicine, Faculty of Medicine University of T, 医学部・衛生学教室, 助手 (90009994)
MANABE Shigeo Department of Hygiene & Preventive Medicine, Faculty of Medicine University of T, 医学部・衛生学教室, 助教授 (90165928)
石川 晋介 , 医学部衛生学教室, 助手 (80168195)
荒川 泰昭 , 医学部衛生学教室, 助手 (40134522)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1985: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | Metal-binding substance / Chromium-binding substance / Nickel-binding substance / Glucose tolerance factor / Metal carcinogenesis / Nickel carcinogenesis / 有機スズの抗癌作用 / ニッケル結合生体内物質 / 金属トランスフォーメーション / クロム結合物質 / 有機錫の抗癌作用 |
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| Research Abstract |
1. Low-molecular-weight (MW:1500)-chromium binding substances were purified from the liver and colostrum of dogs, rabbits and cows. They were composed of glutamic acid, glycine and cysteine with a Cr/amino-terminal residue ratio of 4:1. Chromium bound to them showed a lower toxicity and higher rates of urinary excretion than inorganic chromium compounds. Furthermore, some fraction of purified substances showed in vitro activities comparable to those of glucose tolerance factor in relation to insulin action.
2. A low-molecular-weight (MW:900)-nickel-binding substance was also purified from the liver of rats. Nickel bound to it showed a lower cytotoxicity in the colony-formation tests using BALB/C 3T3 cells than inorganic nickel compounds. The substance.combined nickel in vitro to form the saturated ones with a Ni/molecule ration of 1:1. Some fractions of nickel were replaced with an essential element such as copper or zinc, but not with a non-essential element inclusing cadmium, lead and chromium.
3. Organotin compounds, triphenyl and tributyltins, showed to inhibit insulin release from pancreas, collagen-induced aggregation of platelets, O_2^- production and chemotaxis of leukocytes, and histamine release from mast cells. A common mechanism seemed to be an inhibition of the stimulusresponse coupling in the cell membrane. The same mechanism was supposed to be acting in the anti-malignant tumor activity in vivo and in vitro of dibutyltin compounds.
4. Nickel bound to the low-molecular-nickel-binding substance showed a strong carcinogenic activitiy to cultured BALB/C 3T3 cells in contrast to no induction of transformation by inorganic nickel compounds.
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