Industrial chemicals induced neural apoptosis with its relation to active oxygen species
| Project/Area Number |
07807041
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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 |
Hygiene
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
OGAWA Yasutaka The Jikei University School of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 助手 (60167319)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Yoko Kansai Medical University, Faculty of Medicine, Lecturer, 医学部, 講師 (50193438)
OIKAWA Sinji The Jikei University School of Medicine, Faculty of Medicine, Assistant, 医学部, 助手 (10277006)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Active oxygen species / Apoptosis / Neurotoxicity / Mouse / Dorsal root ganglion / 2,5-Hexanedione / Cisplatin / 後根神経節 / DNA |
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| Research Abstract |
Aim of our study is to investigate the process relating to neurotoxicity of industrial chemicals accompanied by neuronal apoptosis. The hypothesis we are based on is that under the chemical assault apoptosis of neurons will be induced by active oxygen species.
Chemical substances we used were 2,5-hexanedione and cisplatin. 2,5-Hexanedione is well known neurotoxic substance which is a metabolite of n-hexane and methyl n-butyle ketone. It affects axons and its pathology is well-known by axonal swelling filled with neurofilaments. Cisplatin is used as anti-cancer drug and its neurotoxicity is specific to sensory nerves. Material used were Primary culture neurons were used as materials which is believed to have more in vivo characters. Also single strand DNA was used to measure the direct effect of the chemicals to DNA.
The results were as follows ;
(1) 2,5-Hexanedione induced fragmentation of DNA in mouse dorsal root ganglion neurons.
(2) Cisplatin induced fragmentation of DNA in mouse dorsal root ganglion neurons.
(3) 2,5-Hexanedione did not directly affect DNA strands nor induced active oxygen radicals
(4) Cisplatine did not directly affect DNA strands nor induced active oxygen radicals
To study further, we tried to detect DNA ladder in cultured cell. We got the ladder from 2,5-hexanedione induced apoptosis but the level was very week and needs further amplification. Antioxidant substances protected neuronal cell death by cisplatin but could not detect active oxygen species itself.
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Report
(3 results)
Research Products
(10 results)
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[Publications] Endo-Ichikawa, Y., Kohno, H., Furukawa, T., Ueda, T., Ogawa, Y., Tokunaga, R., Taketani, S: "Requirement of multiple DNA-protein interactions for inducible expression of RNR3 gene in Saccharomyces cerevisiae in response to DNA damage" Biochemical and Biophysical Research Communications. 222. 280-286 (1996)
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