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Extracts from cigarette smoke induce DNA damage and cell adhesion molecule expression through different pathways.
Haw-Wen Chen1, Miao-Lin Chien, Yu-Han Chaung
1Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan.
Chemico-Biological Interactions
|November 25, 2004
Summary
Non-fractionated water-soluble cigarette smoke extract (NFWS CSE) causes DNA damage and increases cellular adhesion molecules in HUVECs. Antioxidants prevent DNA damage, but not adhesion molecule changes, suggesting different mechanisms.
Area of Science:
- Endothelial Cell Biology
- Toxicology
- Molecular Mechanisms of Disease
Background:
- Cigarette smoke is a significant risk factor for cardiovascular diseases like atherosclerosis and lung cancer.
- Endothelial dysfunction plays a critical role in the pathogenesis of these diseases.
Purpose of the Study:
- To investigate the impact of non-fractionated water-soluble cigarette smoke extract (NFWS CSE) on DNA damage.
- To examine the effect of NFWS CSE on the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human umbilical vein endothelial cells (HUVECs).
Main Methods:
- HUVECs were exposed to varying doses of NFWS CSE.
- DNA damage was assessed using the comet assay.
- Surface expression of ICAM-1 and E-selectin was quantified via flow cytometry.
- Cells were pretreated with antioxidants (ascorbic acid, alpha-tocopherol) or a metal chelator (1,10-phenanthroline).
Main Results:
- NFWS CSE induced DNA damage in a dose-dependent manner.
- Ascorbic acid and alpha-tocopherol completely protected against NFWS CSE-induced DNA damage.
- NFWS CSE upregulated the surface expression of ICAM-1 and E-selectin.
- Antioxidants did not inhibit NFWS CSE-induced adhesion molecule expression.
- 1,10-phenanthroline partially suppressed ICAM-1 and E-selectin expression.
Conclusions:
- NFWS CSE induces DNA damage and upregulates adhesion molecules in HUVECs.
- Reactive oxygen species are implicated in NFWS CSE-induced DNA damage.
- The mechanisms underlying NFWS CSE-induced DNA damage and adhesion molecule expression appear distinct, with ROS playing a role in the former but not the latter.