Impact of Smoking on p65 Nuclear Factor κB, p38 Mitogen-Activated Protein Kinase, and Inducible Nitric Oxide Synthase Expression Levels in Oral Mucosa

Objectives: Smoking plays an important role in oral cancer development; however, the molecular carcinogenesis mechanism in oral mucosa is not well understood. The aim of this study was to examine and compare the levels of p65 nuclear factor kappa B (NF-kappa B), p38 mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS) expressions between oral mucosa of nonsmoker and smoker volunteers. Methods: Oral cheek mucosa was collected from 78 volunteers. Smokers were divided into 2 subgroups: light smokers (<40 pack years) and heavy smokers (>= 40 pack years). Paraffinized tissue immunochemistry was carried out for p65 NF-kappa B, p38 MAPK, and iNOS expression with specific antibodies. Results were evaluated based on diffuseness and intensity of staining. Results: Group 1 composed of 40 nonsmokers: 52.5% were female and 47.5% were male, with a mean age of 46.4 years. Group 2 composed of 38 smokers (20 light smokers, 18 heavy smokers): 39.5% were female and 60.5% were male, with a mean age of 48.9 years. Total immunohistochemical staining scores of smokers were significantly higher compared with those of nonsmokers in p65 NF-kappa B, p38 MAPK, and iNOS expression (P < 0.001). The highest p65 NF-kappa B, p38 MAPK, and iNOS expression levels were detected in the oral mucosa of heavy smokers. The expression of iNOS and p65 NF-kappa B in heavy smokers was significantly higher compared to that in light smokers (P < 0.01 and P < 0.05, respectively). Although p38 MAPK expressions were higher in heavy smokers compared with light smokers, the difference was not statistically significant (P 9 0.05). Conclusions: Our results show for the first time the significant increase in the expression of p65 NF-kappa B and p38 MAPK in the oral mucosa of smokers. Levels of p65 NF-kappa B, p38 MAPK, and iNOS expression in the oral mucosa of smokers were related to the number of pack years.