Extracts from cigarette smoke induce DNA damage and cell adhesion molecule expression through different pathways

Extracts from cigarette smoke induce DNA damage and cell adhesion molecule expression through different pathways
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DOI:
10.1016/j.cbi.2004.09.014
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发表时间:
2004-12-07
影响因子:
5.1
通讯作者:
Wang, TS
Wang, TS
中科院分区:
医学2区
文献类型:
--
作者:
Chen, HW;Chien, ML;Wang, TS

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香烟烟雾是人类疾病的主要危险因素,如肺癌和动脉粥样硬化。本研究旨在探讨非分级水溶性香烟烟雾提取物(NFWS CSE)对人脐静脉内皮细胞(HUVECs)DNA损伤和细胞粘附分子表达的影响。采用彗星试验和流式细胞术分别检测DNA损伤和细胞间粘附分子-1(ICAM-1)和E-选择素(E-selectin)的表达。NFWS CSE在2 h暴露期间以剂量依赖性方式诱导DNA损伤。用抗坏血酸或α-生育酚预处理完全抑制NFWS CSE诱导的DNA损伤。NFWS CSE暴露还上调HUVECs表面ICAM-1和E-选择素的表达。用抗坏血酸或α-生育酚预处理对NFWS CSE诱导的E-选择素和ICAM-1表达没有影响。相比之下,非抗氧化剂金属螯合剂1,10-菲咯啉部分抑制ICAM-1和E-选择素的表面表达。这些结果表明,NFWS CSE暴露诱导HUVEC中DNA损伤和粘附分子的表面表达。然而,这些作用的分子机制可能是通过不同的途径:活性氧参与了NFWS CSE诱导的DNA损伤,但与NFWS CSE诱导的E-选择素和ICAM-1表达关系不大。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Cigarette smoke is major risk factor for human diseases, such as lung cancer and atherosclerosis. The present study was undertaken to investigate the effect of non-fractionated water-soluble cigarette smoke extract (NFWS CSE) on DNA damage and cellular adhesion molecule expression in human umbilical vein endothelial cells (HUVECs). DNA damage and the surface expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by the use of the comet assay and flow cytometry, respectively. NFWS CSE-induced DNA damage in a does-dependent manner during a 2 h exposure. Pretreatment with ascorbic acid or alpha-tocopherol completely inhibited the NFWS CSE-induced DNA damage. NFWS CSE exposure also up-regulated the surface expression of ICAM-1 and E-selectin in HUVECs. Pretreatment with ascorbic acid or alpha-tocopherol had no effect on NFWS CSE-induced E-selectin and ICAM-1 expression. In contrast, the non-antioxidant metal chelator 1,10-phenanthroline partially suppressed the surface expression of ICAM-1 and E-selectin. These results suggest that NFWS CSE exposure induces both DNA damage and the surface expression of adhesion molecules in HUVECs. However, the molecular mechanism of these effects may be through different pathways: reactive oxygen species are involved in NFWS CSE-induced DNA damage but have little relation to NFWS CSE-induced E-selectin and ICAM-1 expression. (C) 2004 Elsevier Ireland Ltd. All rights reserved.