Whole DNA methylome profiling in mice exposed to secondhand smoke. Mus musculus

A large body of evidence has linked secondhand smoke (SHS) to lung cancer in nonsmokers. Yet, the underlying mechanisms of SHS carcinogenicity in nonsmokers' lung cancer remain elusive. Recently, we have demonstrated a genotoxic mode of action for SHS, based on the ability of this carcinogen to induce adduct-driven mutagenesis in transgenic Big Blue® mice. In the present study, we have expanded this investigation to determine whether SHS can also cause epigenetic effects through aberrations of DNA methylation. Here, we have globally profiled DNA methylation in the lung of Big Blue® mice exposed to SHS for a duration of 4-months, both immediately after the termination of exposure and at several intervals post-exposure. Overall design: We have used a genome-wide microarray-based approach to catalogue DNA methylation profile in the lung of mice exposed to SHS and at various recovery periods from the time of exposure. Mice exposed to clean air, for comparable amount of times, were used as controls. Mice that were injected intraperitoneally with chronic doses of B(a)P (a powerful carcinogen in SHS) or DMSO (sham) were used for comparison purposes .