| Project/Area Number |
61480164
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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 |
Hygiene
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| Research Institution | Dept. Hygiene, School of Medicine, Kanazawa University |
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Principal Investigator |
HASHIMOTO Kazuo Dept. Hygiene, School of Medicine, Kanazawa University, 医学部, 教授 (30092795)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Junko Dept. Hygiene, School of Medicine, Kanazawa University, 医学部, 助手 (90110626)
TANII Hideji Dept. Hygiene, School of Medicine, Kanazawa University, 医学部, 助手 (90110618)
HAYASHI Masao Dept. Hygiene, School of Medicine, Kanazawa University, 医学部, 助教授 (70164960)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | Chemicals / Acrylamide derivatives / Inorganic metals / Neuronal cell culture / Structure-neurotoxicity / 構造一活性相関 / 神経毒性予測 / ラット胎児神経細胞培養 / アルコール / 神経毒性 / イオンポテンシャル / ケミカルソフトネス / 金属 / セキ髄神経節 / ニューロブラストーマ / シュハノーマ / 神経培養細胞 / 小脳星状膠細胞 / 中毒性神経障害 / 作用機序 / 毒性予測 / 神経細胞培養 / シュバノーマ |
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| Research Abstract |
There have been many incidences of toxic neuropathies due to industrial chemicals environmental pollutants, drugs, insecticides and other chemicals. It is very important to prevent these diseases, since neuropathies are sometimes severe and irreversible. The present study was done to examine the mechanisms of neurotoxic action and to predict the neurotoxicity of chemicals. The results obtained are as follows:
1. It has been suggested that either the direct action to neurofilaments or to Ca^<2+> acitivated neutral protease is related to the neurotoxicity of chemicals.
2. Neurotoxic acrylamide derivatives inhibited dose-dependently the neurite outgrowth from retinal explant culture, but non-neurotoxic ones did not show any effect on the growth.
3. Neurotoxic acrylamide derivatives caused degeneration of mouse neuroblastoma cells and inhibition of cell growth, but only inhibition of cell growth in rat Schwannoma cells. These chemicals inhibited more the immature cells than the mature cells.
4. Growth of cerebellar astrocytes from rat embryo was dose-dependently inhibited by acrylamide derivatives, and the inhibition was postulated to be caused by that of cell division.
5. Protein content, lactic dehydrogenase activity and glucose consumption of neuronal cells from rat embryo were all inhibited dose-dependently by neurotoxic acrylamide derivatives. This culture system seems to be appropriate for neurotoxicity assessment.
6. Primary neuronal cell culture from rat embryo was vulnerable to acetaldehyde, which was the main metabolite of ethanol. The inhibitory effect of acetaldehyde was protected by thiol compounds such as reduced glutathione.
7. Inorganic metals inhibited dose-dependently growth of cultured neuronal cells and astrocytes. The effect was significantly correlated with chemical softness of the metals.
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