Smokers and passive smokers gene expression profiles: correlation with the DNA oxidation damage.
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.
Lodovici
Maura
M
Department of Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. maura.lodovici@unifi.it
Luceri
Cristina
C
De Filippo
Carlotta
C
Romualdi
Chiara
C
Bambi
Franco
F
Dolara
Piero
P
D000293:Adolescent; D000328:Adult; D004249:DNA Damage / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D025341:Principal Component Analysis; D012907:Smoking / Q000235:genetics / Q000378:metabolism*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D015854:Up-Regulation
D014028:Tobacco Smoke Pollution