Smokers and passive smokers gene expression profiles: Correlation with the DNA oxidation damage

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• 作者：Maura Lodovici ; Cristina Luceri ; Carlotta De Filippo ; Chiara Romualdi ; Franco Bambi ; Piero Dolara
• 刊名：Free Radical Biology and Medicine
• 出版年：2007
• 出版时间：1 August 2007
• 年：2007
• 卷：43
• 期：3
• 页码：415-422
• 全文大小：891 K

文摘

Healthy volunteers (n = 50) were enrolled for studying the variation of gene expression induced by smoking in peripheral lymphocytes. RNAs from smokers (> 3 cigarettes/day, n = 20) and passive smokers (exposed to tobacco smoke > 3 h/day, n = 10) were hybridized versus a reference pool obtained by mixing equal amounts of RNA from 20 nonsmokers, and gene expression was analyzed using DNA microarrays containing 13,971 oligos. Principal component analysis showed that 99.7 % of gene expression variability was related to plasma cotinine, age, and DNA oxidation damage. SAM and GenMAPP/MAPPFinder analyses showed that smokers, compared to nonsmokers, had 129 down-regulated and 87 up-regulated genes, whereas passive smokers, compared to nonsmokers, had 44 down-regulated and 159 up-regulated genes, mainly involved in pathways associated with the activation of defensive responses. Hierarchical cluster analysis identified two distinct clusters of smokers, characterized by different oxidative DNA damage: smokers with high DNA oxidation damage, compared to smokers with low DNA oxidation damage, had a large number (150) of down-regulated genes, mainly associated with xenobiotic metabolism, DNA damage and repair, inflammatory responses, lymphocyte activation, and cytokine activity, suggesting a reduced cellular response to toxic agents in this subset of smokers that could lead to an increased DNA oxidation damage.