1988 Fiscal Year Final Research Report Summary
Mechanisms of action and prediction of neurotoxicity for chemical substances
| 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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| Keywords | Chemicals / Acrylamide derivatives / Inorganic metals / Neuronal cell culture / Structure-neurotoxicity / 構造一活性相関 / 神経毒性予測 |
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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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