Diesel exhaust particle-induced cell death of human leukemic promyelocyticcells HL-60 and their variant cells HL-NR6

Citation
M. Matsuo et al., Diesel exhaust particle-induced cell death of human leukemic promyelocyticcells HL-60 and their variant cells HL-NR6, BIOL PHAR B, 24(4), 2001, pp. 357-363
Citations number
22
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN journal
09186158 → ACNP
Volume
24
Issue
4
Year of publication
2001
Pages
357 - 363
Database
ISI
SICI code
0918-6158(200104)24:4<357:DEPCDO>2.0.ZU;2-A
Abstract
The cytotoxicity of diesel exhaust particles (DEPs) toward human leukemic p romyelocytic cells HL-60 was examined, DEPs were toxic and cytotoxicity inc reased in a dose-dependent manner. All cells died with 750 mug/ml DEPs in c ulture media, Apoptosis occurred in HL-60 cells exposed to DEPs, The cytoto xicity of DEP extracts with organic solvents was much lower than those of D EPs and organic solvent-washed residual DEPs, HL-NR6 cells, an HL-60 varian t cell line, having higher superoxide dismutase and catalase activities tha n HL-60 cells, were more resistant to DEP cytotoxicity. When preincubated w ith the fluorescent probe diacetoxymethyl 6-carboxy-2',7'-dichlorodihydrofl uorescinate diacetate and then exposed to DEPs, HL-60 cells emitted green f luorescence under blue illumination, indicating that reactive oxygen specie s were generated within the cells. The DEP cytotoxicity correlated inversel y with the cellular concentration of reduced glutathione (GSH), which had b een attenuated with L-buthionine-(R,S)-sulfoximine, a gamma -glutamylcystei ne synthetase inhibitor, and was lowered with ethyl reduced glutathionate, a GSH carrier across biomembranes, Further, DEPs themselves decreased the c ellular concentration of GSH in a dose-dependent manner, The alpha -tocophe rol model compound 2,2,5,7,8-pentamethylchroman-6-ol decreased DEP cytotoxi ciy, while alpha -tocopherol had no effect. In addition, quinacrine, an end ocytosis 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.