ABSTRACT Tobacco is smoked by people worldwide. Burning tobacco results in combustion, pyrolysis, and other chemical reactions that expose the smoker to thousands of chemicals, causing harm. Several modes of action are involved in the toxicology of tobacco smoke, including epigenetic mechanisms. These epigenetic changes include methylation of DNA by covalent addition of a methyl group to the cytosine residue in a CpG site; posttranslational modification of amino tails of histones; and aberrant expression of microRNAs. Together, these major epigenetic mechanisms can affect whether a gene or set of genes is silenced or activated, which can lead to disruption in cellular function and cause a variety of diseases. Although epigenetic profiling is not yet recognized in toxicological sciences as a valid biomarker of potential hazardous effects of environmental agents, there is now a growing body of evidence that environmental exposures can induce epigenetic changes. In fully assessing the toxicologic impact of tobacco smoke, its epigenetic action should be considered. The effect of tobacco smoke by each of the major epigenetic mechanisms will be described in this review. Its effect involving DNA methylation has been the most studied, examining both global effect and specific gene targeting. Included in the discussion will be observations from disease studies in human populations and those involving animal models and in vitro cell culture systems. There are also several examples in which the epigenetic effects of individual constituents of tobacco smoke have been tested. Limitations of the available data and future challenges and opportunities will be addressed.
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