| Project/Area Number |
16209021
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Osaka City University |
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Principal Investigator |
ENDO Ginji Osaka City University, Graduate School of Medicine, Professor (20160393)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Kazuhiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor (70323293)
FUSHIKI Shinji Kyoto Prefectural University of Medicine, Graduate School, Professor (80150572)
SUZUKI Tsutomu Hoshi University, The Faculty of Pharmaceutical Sciences, Professor (90130757)
YAMANAKA Kenzo Nihon University, College of Pharmacy, Associate Professor (50182572)
WANIBUCHI Hideki Osaka City University, Graduate School of Medicine, Professor (90220970)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
Fiscal Year 2006: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2005: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2004: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
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| Keywords | diphenylarsinic acid / oreano-arsenic / chemical weanon / environmental nollution / cerebellar-brainstem symptoms / cerebral symptoms / Poisoning / mental retardation / 環境 / 汚染 / 飲料水 |
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| Research Abstract |
1. We noted a new clinical syndrome with prominent cerebellar-brainstem symptoms such as ataxic gait, titubation and scanning speech, myoclonus and tremor, and cerebral symptoms such as upward gaze-evoked nystagmus, sleep disorder, and memory impairment in residents who had drunk well water contaminated by diphenylarsinic acid (DPAA). Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants.
2. Motor impairment and the down -regulation of the dopamine receptor function in striatum were observed in adult mice treated with DPAA. Motor learning impairment was observed in neonatal mice exposed to a low dose of DPAA.
3. Administration of 20 ppm DPAA for 6 weeks significantly increased the number and areas of glutathione S-transferase placental form positive foci induced by diethylnitrosamine in rats. These results indicated the DPAA exerts promoting hepatocarinogenesis in rats.
4. Pathogenetic observations of DPAA intoxication were the vacuolation of glomerulus in granular layer of cerebellum by microscope, and the axonal degeneration by electron microscope.
5. Significantly positive staining with malondialdehyde and 3-nitrotyrosine was observed in the cerebellar Purkinje cells by repeated administration (5 mg/kg/day) with DPA for 5 weeks that led to the cerebellar symptoms from a behavioral pharmacology standpoint. These results suggest that DPAA associated novel active species may be a factor underlying the oxidative and nitrosative stress in Purkinje cells, and the damage lead to the cerebellar symptpms.
6. A selective and efficient clean-up method with solvent extraction and solid phase extraction for DPAA in fat and brain was developed.
7. We measured urinary arsenic compounds in 142 workers by HPLC-ICP-MS. DPAA peaks were detected in none of the workers.
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