Wood smoke particles generate free radicals and cause lipid peroxidation, DNA damage, NFκB activation and TNF-α release in macrophages

被引:81
作者
Leonard, SS
Wang, SW
Shi, XL
Jordan, BS
Castranova, V
Dubick, MA
机构
[1] NIOSH, Hlth Effects Lab Div, Pathol & Physiol Res Branch, Morgantown, WV 26505 USA
[2] W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26505 USA
[3] USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA
关键词
wood smoke; free radicals; DNA damage;
D O I
10.1016/S0300-483X(00)00256-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present study investigated the generation of free radicals by wood smoke and cellular injuries caused by these radicals. Wood smoke was collected after thermolysis of western bark. Electron spin resonance (ESR) techniques were used to measure both carbon-centered radicals and generation of reactive oxygen species (ROS) by wood smoke. Wood smoke, in the presence of H2O2, was found to be able to generate hydroxyl radical ((OH)-O-.). DNA strand breakage was measured by exposing wood smoke to lambda Hind III fragments using gel electrophoresis. Wood smoke combined with H2O2 caused DNA damage. Sodium formate, an (OH)-O-. radical scavenger, or deferoxamine, a metal chelator, inhibited the DNA damage. Cellular DNA damage was also measured in cultured RAW 264.7 mouse macrophage cells by the single cell gel (SCG) electrophoresis assay. Cells were exposed to wood smoke samples for various times and significant DNA damage was observed. Elemental analysis was performed on the filter samples and the presence of Fe was noteworthy. Wood smoke is also able to cause lipid peroxidation, activate nuclear transcription factor, NF kappa B, and enhance the release of TNF-alpha from RAW 264.7 cells. The results indicate that the free radicals generated by wood smoke through the reaction of Fe with H2O2 are able to cause DNA and cellular damage and may act as a fibrogenic agent. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:147 / 157
页数:11
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