| Project/Area Number |
59480124
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | National Institute of Hygienic Sciences. |
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Principal Investigator |
TAKAHASHI Atsushi Head, Division of Medical Chemistry, National Institute of Hygienic Sciences., その他, 研究員 (20111106)
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| Co-Investigator(Kenkyū-buntansha) |
OMORI Yoshihito President, Biological Safety Research Center, National Institute of Hygienic Sci, センター長 (50079307)
KAWANISHI Toru Researcher, Section of biochemical Pharmacology, Biological Safety Research Cent, 薬理部, 研究員 (40124383)
OHNO Yasuo Chief, Section of biochemical Pharmacology, Biological Safety Research Center, N, 薬理部, 室長 (30111107)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1986: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1985: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1984: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Renal cells / Freshly isolated renal cells / 腎毒性 / 実験モデル |
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| Research Abstract |
For the purpous to establish freshly isolated renal cells as a in vitro test method of toxicity evaluation, we improved the method of Jones'(1979) and obtained the cells with high viability ( >95%) and yield (Ca <10^8> cells/rat). This preparation had a high activity of the enzymes which existed predominantly in proximal renal tubular epithelial cells. Most of the cells bound with monoclonal antibody which was specific to the epithelial cells. These results indicated that most of the cells were originated from this region of the kidneys. Parathyroid hormon increased cAMP content of the renal cells.
Carriar of the organic anion was shown to exist in the cell membrane using 8-anilino 1-naphthalene sulfornate. Aminopyrine metabolizing activities of the renal cells were about 0.4% of those of hepatocytes. Toxic effects of chemicals were : 1 ) Direct acting agents, such as <HgCl_2> , <CdCl_2> , and disulfiram, caused the loss of viability of the cells. Although the effects of disulfiram were inhibited by GSH, those of <CdCl_2> were not inhibited completely by cysteine and GSH. 2 ) Effects of gentamycin were not observed, but adriamycin decreased the GSH content of the cells. 3 ) Cyclophosphamide and paracetamol, which were known to be activated metabolically by cyt. P-450 linked drug metabolizing system, did not have toxic effects. 4 ) Toxicity of allyl alcohol were marked in female rats, in which activity of alcohol dehydrogenase were higher than in male rats.
These results indicated that the renal cell preparation could be used to study the mechanism of acute toxicity of chemicals.
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