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Abstract

Disastrous effects of tobacco consumption on health remain in the focus of preclinical and clinical research. Exposures to tobacco smoke are closely connected to acute and chronic smoke lung dysfunctions and the effects are not restricted to airway inflammation processes. The facts that smoke exposure result in aberrant gene expression and changes in cellular phenotype resulting in clinical patterns. Here we pyrolyzed constituents of tobacco smoke, induced a stress response in human embryonic lung (HEL) cells, which respond with an altered expression of a broad spectrum of genes. We systematically analyzed the genetic expression, using the microarraytechnology. After exposure of HEL cells to alkaline or acidic extracts of pyrolyzed smoke, already 2h after exposition the most affected genes (HMOX1, CYP1B1, ID3, and ID2) were rapidly up-regulated, whereas after 24 hours the genes were almost downregulated. Using DAVID bioinformatics we detected annotation clusters with significant enrichment scores allowing insight into pharmacological processes and molecular functions. In the alkaline and acidic probes in a ratio 24 h versus 2h we identified annotation clusters with enrichment scores (between 5.77 and 2.89) representing upregulated genes. A negative transcription control leads to the conclusion that a "loss of function" can be possible. STRING tools give insight into the functional network of the gene products of affected genes. Noticeable is the fact that the detected genes with late response encode predicted proteins with unknown function (LOC100134504, LOC645157, LOC653156). With Blast2GO we generated and analysis and graphs of reliable functions. INTRODUCTION: The WHO reported in 2011 data on the global tobacco epidemic and admonished of the danger and the consequences of the tobacco smoke: Up to half of all tobacco users will die from tobacco-raised disease. Twelve milli