Effects of Tobacco Smoke on Mononuclear Blood Cell Gene Ontologies

Objectives: Alterations of the host response by tobacco smoke adversely affect the periodontium. In this study, we examined the effects of in vitro acute smoke exposure on inflammatory and neoplastic pathways (ontologies) using microarray m-RNA expression of the complete genome. Methods: Peripheral blood mononuclear cells were isolated from 9 medically healthy nonsmokers and exposed or not exposed to in vitro smoke (baseline controls), then the m-RNA was isolated, amplified and quantified on gene microarrays. To identify genes in specific ontologies/pathways most relevant to periodontal inflammatory and neoplastic conditions in the mouth, two analytical approaches were employed 1. Genes with previously known relevance to periodontal inflammation or oral neoplasia were examined for significant alterations of expression with smoke (paired t-test) 2. A Statistical Analysis of Microarrays (SAM) was used to identify any of the total 30,000 genes with significantly altered expression (882 genes in total/ delta .66). Gene ontologies with greater than 10% altered genes were considered significantly altered ontologies (Go Miner statistical program). Results: There was a significant elevation genes encoding for IL-1 beta synthesis (W47101: 1.57±.93 and AA150507: 1.79±.95) and IL-15 (1.41±.69) and several oncogenes including GR01 (W42743: 2.85±2.10: W46900: 2.23±1.75) (p<0.05) and a depression of Interferon regulatory factor 7 (AA 443090: 0.37±1.06) (p<0.05). Among the 2,468 ontology groups (AMIGO classification) 87 had a significant proportion of altered expressed genes including ontologies involved in cell death and apoptosis, regulation of cytokine synthesis, signaling pathways, and chemotaxis. Conclusions: These observations provide a framework for a comprehensive and systematic approach to the study of tobacco on the periodontal host response and oral neoplasia.