Tobacco Heating System 2.2 has a limited impact on DNA methylation of candidate enhancers in mouse lung compared with cigarette smoke.
Food Chem Toxicol
; 123: 501-510, 2019 Jan.
Article
in En
| MEDLINE
| ID: mdl-30414959
Cigarette smoke (CS) exposure has been shown to correlate with changes in DNA methylation levels, however, the impact of CS on DNA methylation at genome-wide scale is missing. Here, we used whole-genome bisulfite sequencing to assess the effects of CS extract and aerosol from the Tobacco Heating System (THS) 2.2, a candidate modified risk tobacco product, on DNA methylation in lung and liver tissues from apolipoprotein E-deficient mice during an eight-month period of exposure. We found that in lung tissue, CS mainly induced hypermethylation of candidate enhancers at late time points, while promoters were less affected. This effect was strongly reduced upon cessation or switching to THS 2.2. By contrast, chronic exposure to THS 2.2 had a limited effect on DNA methylation at both promoters and enhancers. We also identified members of the Ets and Fox families of transcription factors as potential players in the epigenetic response to CS exposure in lung tissue. In contrast to the lung, DNA methylation in the liver was largely insensitive to all investigated exposures. In summary, our investigations indicate that CS-related DNA methylation alterations are tissue-specific, occur mainly at enhancers and are strongly reduced upon smoking cessation or switching to THS2.2.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Smoke
/
Nicotiana
/
Smoking
/
Enhancer Elements, Genetic
/
DNA Methylation
/
Tobacco Products
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Food Chem Toxicol
Year:
2019
Document type:
Article
Affiliation country:
Switzerland
Country of publication:
United kingdom