A Multi-omics Study of Epigenetic Changes in Type II Alveolar Cells of A/J Mice Exposed to Environmental Tobacco Smoke
Lung cancer remains a major contributor to cancer fatalities, with cigarette smoking known to be responsible for up to 80% of cases. Based on the ability of cigarette smoke to induce inflammation in the lungs and increased lung cancer incidence in smokers with inflammatory conditions such as COPD, we hypothesized that inflammation plays an important role in carcinogenicity of cigarette smoke. In order to test this hypothesis, we performed multi-omic analyses of Type II pneumocytes of A/J mice exposed to cigarette smoke for various time periods. We found that cigarette smoke exposure resulted in significant changes in DNA methylation and hydroxymethylation, gene expression patterns, and protein abundance that were partially reversible and contributed to an inflammatory and potentially oncogenic phenotype. Overall design: Male and female A/J mice were treated with cigarette smoke or filtered air for 3 weeks, 10 weeks and 10 weeks followed by 4 weeks recovery. There are three mice in each treatment group. The mice were sacrificed after treatment and Alveolar type II epithelial cells (Type II pneumocytes) were isolated from the harvested lung tissues. DNA and RNA were extracted from the isolated Alveolar type II epithelial cells. DNA were used for genome wide mapping of 5mC and 5hmC and RNA were used for RNA-seq.