Diesel Exhaust Particle-Induced Cell Death of Human Leukemic Promyelocytic Cells HL-60 and Their Variant Cells HL-NR6
スポンサーリンク
概要
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The cytotoxicity of diesel exhaust particles(DEPs) toward human leukemic promyelocytic cells HL-60 was examined. DEPs were toxic and cytotoxicity increased in a dose-dependent manner. All cells died with 750 μg/ml DEPs in culture media. Apoptosis occurred in HL-60 cells exposed to DEPs. The cytotoxicity of DEP extracts with organic solvents was much lower than those of DEPs and organic solvent-washed residual DEPs. HL-NR6 cells, an HL-60 variant cell line, having higher superoxide dismutase and catalase activities than HL-60 cells, were more resistant to DEP cytotoxicity. When preincubated with the fluorescent probe diacetoxymethyl 6-carboxy-2', 7'-dichlorodihydrofluorescinate diacetate and then exposed to DEPs, HL-60 cells emitted green fluorescence under blue illumination, indicating that reactive oxygen species were generated within the cells. The DEP cytotoxicity correlated inversely with the cellular concentration of reduced glutathione(GSH), which had been attenuated with L-buthionine-(R, S)-sulfoximine, a γ-glutamylcysteine synthetase inhibitor, and was lowered with ethyl reduced glutathionate, a GSH carrier across biomembranes. Further, DEPs themselves decreased the cellular concentration of GSH in a dose-dependent manner. The α-tocopherol model compound 2, 2, 5, 7, 8-pentamethylchroman-6-ol decreased DEP cytotoxicity, while α-tocopherol had no effect. In addition, quinacrine, an endocytosis inhibitor, decreased DEP cytotoxicity. These results show that DEPs are cytotoxic and suggest that the cytotoxicity results from generation of reactive oxygen species by DEPs which have been incorporated into cells.
- 公益社団法人日本薬学会の論文
- 2001-04-01
著者
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Sagai Masaru
Division Of Nursing And Human Sciences Faculty Of Health Sciences Aomori University Of Health And We
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Shimada Toshio
Department of Cardiology, Shimane University School of Medicine
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Utsumi Kozo
Institute Of Medical Science Kurashiki Medical Center
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Shimada T
Department Of Biology Faculty Of Science And High Technology Research Center Konan University
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Suzuki Motohisa
Graduate School Of Health Sciences University Of Shizuoka
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Utsumi Kozo
Dep. Of Cytology And Histology Okayama Univ. Graduate School Of Medicine Dentistry And Pharmaceutica
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YABUKI Munehisa
Institute of Medical Science, Center for Adult Diseases
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Yabuki Munehisa
Institute Of Medical Science Kurashiki Medical Center
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MATSUO Mitsuyoshi
Department of Biology, Faculty of Science and High Technology Research Center, Konan University
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UENISHI Rie
Department of Biology, Faculty of Science and High Technology Research Center, Konan University
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YAMANAKA Suzuka
Department of Biology, Faculty of Science and High Technology Research Center, Konan University
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Uenishi Rie
Department Of Biology Faculty Of Science And High Technology Research Center Konan University
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Matsuo Mitsuyoshi
Department Of Biology Faculty Of Science And High Technology Research Center Konan University
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Sagai Masaru
Division Of Human Sciences Faculty Of Health Sciences Aomori University Of Health And Welfare
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Yamanaka S
Department Of Biology Faculty Of Science And High Technology Research Center Konan University
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Shimada Toshio
Department of Biology, Faculty of Science and High Technology Research Center, Konan University
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