Comparison of the effects on the ApoE^-/- mouse lung epigenome of exposure to the aerosol of a candidate Reduced Risk Product, THS2.2, with exposure to conventional cigarettes smoke

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Smoking cigarettes is a major risk factor in the development and progression of cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). Candidate Reduced Risk Products (RRPs) are being developed to reduce smoking-related health risks. We investigated over an 8-month period the effects of exposure to cigarette smoke (CS) or to the aerosol of a candidate RRP, Tobacco Heating System (THS) 2.2, on DNA methylation in the lung of apolipoprotein E-deficient mice. Cessation or switching to THS2.2 after 2 months of CS exposure were also assessed. High-throughput sequencing of bisulfite treated DNA revealed a gradual increase in the number of hypermethylated CpG loci in DNA extracted from lungs of mice exposed to CS. The number of hypermethylated CpG loci after 2 month exposure to THS2.2 (nicotine concentration matched to CS) also increased, however, hypermethylation was limited from 3 month on. Cessation or switching to THS2.2 resulted in a decrease in the number of hypermethylated CpG loci. In this mouse model initial exposure to CS or THS2.2 resulted in hypermethylation of CpG loci in lung. Continuous exposure to CS further increased the number of hypermethylated CpG loci while continuous exposure to THS2.2 reverted the CpG methylation level to the level observed in the lung of mice exposed to fresh air. Likewise, cessation or switching to THS2.2 reverted the hypermethylation of CpG loci.

Reduced Risk Products (“RRPs”) is the term we use to refer to products with the potential to reduce individual risk and population harm in comparison to smoking cigarettes.