Tobacco smoking-response genes in blood and buccal cells

•A biological monitoring was performed to find tobacco smoking- specific toxic mechanisms in surrogate and non-invasive tissues.•The Fcγ-receptor mediated phagocytosis and leukocyte transendothelial migration pathways were differentially expressed between smokers and nonsmokers.•The ACTG1, involved in the maintenance of actin cytoskeleton, cell migration and cancer metastasis, was highly expressed in both of blood and buccal cells.•Smokers showed high levels of urinary malondialdehyde (MDA) and down-regulation of expressions of antioxidant related genes including TPO, MPO, GPX2, PTGR1, and NUDT1.

Tobacco smoking is a well-known cause of various diseases, however, its toxic mechanisms for diseases are not completely understood, yet. Therefore, we performed biological monitoring to find tobacco smoking-responsive mechanisms including oxidative stress in Korean men (N = 36). Whole genome microarray analyses were performed with peripheral blood from smokers and age-matched nonsmokers. We also performed qRT-PCR to confirm the microarray results and compared the gene expression of blood to those of buccal cells. To assess the effects of tobacco smoking on oxidative stress, we analyzed urinary levels of malondialdehyde (MDA), a lipid peroxidation marker, and performed PCR-based arrays on reactive oxygen species (ROS)-related genes. As results, 34 genes were differently expressed in blood between smokers and nonsmokers (ps < 0.01 and >1.5-fold change). Particularly, the genes involved in immune responsive pathways, e.g., the Fcγ-receptor mediated phagocytosis and the leukocyte transendothelial migration pathways, were differentially expressed between smokers and nonsmokers. Among the above genes, the ACTG1, involved in the maintenance of actin cytoskeleton, cell migration and cancer metastasis, was highly expressed by smoking in both blood and buccal cells. Concerning oxidative stress, smokers showed high levels of urinary MDA and down-regulation of expressions of antioxidant related genes including TPO, MPO, GPX2, PTGR1, and NUDT1 as compared to nonsmokers (ps < 0.05). In conclusion, these results suggest that systemically altered immune response and oxidative stress can be tobacco-responsive mechanisms for the related diseases. Based on consistent results in blood and buccal cells, expression of the ACTG1 can be a tobacco smoking-responsive biomarker.

Graphical abstractDownload full-size imageThe most significant biological pathways for the set of smoking correlated genes: (A) the lists of the most enriched pathways which were categorized by KEGG pathways. (B) An integrative network of genes differentially expressed by 1.5-fold change in smokers, compared to nonsmokers.