title: The combined effects of single-nucleotide polymorphisms, tobacco products, and ethanol on normal resting blood mononuclear cells.
abstract: BACKGROUND
  Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals.
  
  
  METHODS
  Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors.
  
  
  RESULTS
  After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 µM nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes.
  
  
  CONCLUSIONS
  Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Section of Oncology, University Hospital , Uppsala, Sweden. lena.cederblad@onkologi.uu.se
authors.forename: Lena
authors.initials: L
authors.lastname: Cederblad
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Mats
authors.initials: M
authors.lastname: Engström
authors.forename: Juan
authors.initials: J
authors.lastname: Castro
authors.forename: Lars Erik
authors.initials: LE
authors.lastname: Rutqvist
authors.forename: Nongnit
authors.initials: N
authors.lastname: Laytragoon-Lewin
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D002453:Cell Cycle; D016923:Cell Death; D004247:DNA / Q000235:genetics; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D012906:Smoke / Q000009:adverse effects; D062789:Tobacco Products / Q000009:adverse effects*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; C413655:KDM4C protein, human; D012906:Smoke; D000431:Ethanol; D009538:Nicotine; D004247:DNA; D056484:Jumonji Domain-Containing Histone Demethylases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2