title: Expression of epigenetic modifiers is not significantly altered by exposure to secondhand smoke.
abstract: OBJECTIVE
  Secondhand smoke (SHS) is a major risk factor for lung cancer in nonsmokers. DNA damage-derived mutagenicity is a well-established mechanism of SHS-carcinogenicity; however very little is known about the impact of SHS exposure on the epigenome.
  
  
  METHODS
  We have investigated whether exposure to SHS can modulate the expression of key epigenetic regulators responsible for the establishment and/or maintenance of DNA methylation and histone modification patterns in vivo. We have sub-chronically exposed mice to a mutagenic but non-tumorigenic dose of SHS, and subsequently determined the expression levels of major epigenetic modifiers in the lungs of SHS-exposed mice, immediately after termination of exposure and following 7-month recovery in clean air.
  
  
  CONCLUSIONS
  Quantification of the expression of genes encoding DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b and Dnmt3l), methyl binding domain proteins (Mecp2, Mbd2 and Mbd3) and histone deacetylases (Hdac1 and Hdac2) by quantitative reverse-transcription polymerase chain reaction analysis showed modest but not statistically significant differences in the relative transcription of these key epigenetic regulators between SHS-exposed mice and age-matched controls. The non-significant changes in the expression of main epigenetic modifiers in SHS-exposed mice imply that SHS may predominantly induce genotoxic effects, particularly at non-tumorigenic doses, whereas epigenetic effects may only be secondary and manifest en route to tumor formation.
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, M/C 9603, Los Angeles, CA 90033, USA. Electronic address: tommasi@med.usc.edu.
authors.forename: Stella
authors.initials: S
authors.lastname: Tommasi
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, M/C 9603, Los Angeles, CA 90033, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, M/C 9603, Los Angeles, CA 90033, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Besaratinia
mesh_terms: D000107:Acetylation; D000818:Animals; D015415:Biomarkers; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D006657:Histones; D014028:Tobacco Smoke Pollution; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: DNA methyltransferases (DNMTs); Epigenome; Histone deacetylases (HDACs); Lung cancer; Methyl-CpG binding domain proteins (MBDs); Nonsmokers