title: Cigarette smoke-induced differential gene expression in blood cells from monozygotic twin pairs.
abstract: Chemical carcinogenesis induced by lifestyle factors like cigarette smoking is a major research area in molecular epidemiology. Gene expression analysis of large numbers of genes simultaneously using microarrays holds the opportunity to study the effects of such an exposure at the genome level yielding more mechanism-based information. Therefore, the aim of our study was to investigate multiple gene expressions in blood, indicative for the effects caused by cigarette smoke. Smoking-discordant monozygotic twin pairs (n=9) were studied to diminish influences of genetic background. Using a dedicated microarray containing 600 toxicologically relevant genes, we investigated which genes are differentially expressed in smokers compared to non-smokers. We also looked for genes of which the expression changes correlated with DNA adducts, a biomarker of effective dose for exposure to cigarette smoke carcinogens. The mean DNA adduct level in smokers differed significantly from that in non-smokers (mean +/- standard error 1.96 +/- 0.24 versus 1.17 +/- 0.16 adducts per 10(8) nucleotides, respectively; P=0.04). The genes of which the expression differed most significantly between smokers and non-smokers are ATF4, MAPK14, SOD2, CYP1B1 and SERPINB2. CYP1B1 and SOD2 can directly be linked to cigarette smoke exposure, whereas the other genes are associated with stress or environmentally induced response. Main functions of the genes influenced by cigarette smoking comprise carcinogen metabolism, oxidative stress response and anti-apoptosis.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Danitsja M
authors.initials: DM
authors.lastname: van Leeuwen
authors.forename: Ebienus
authors.initials: E
authors.lastname: van Agen
authors.forename: Ralph W H
authors.initials: RW
authors.lastname: Gottschalk
authors.forename: Robert
authors.initials: R
authors.lastname: Vlietinck
authors.forename: Marij
authors.initials: M
authors.lastname: Gielen
authors.forename: Marcel H M
authors.initials: MH
authors.lastname: van Herwijnen
authors.forename: Lou M
authors.initials: LM
authors.lastname: Maas
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
authors.forename: Joost H M
authors.initials: JH
authors.lastname: van Delft
mesh_terms: D000199:Actins / Q000235:genetics; D051701:Activating Transcription Factor 4; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016001:Confidence Intervals; D003367:Cotinine / Q000097:blood; D065633:Cytochrome P-450 CYP1B1; D017931:DNA Primers; D004912:Erythrocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14; D015843:Serpins / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase; D014430:Twins, Monozygotic; D000099156:Superoxide Dismutase 2
chemical_list: D000199:Actins; D051701:Activating Transcription Factor 4; D001189:Aryl Hydrocarbon Hydroxylases; D003367:Cotinine; D065633:Cytochrome P-450 CYP1B1; D017931:DNA Primers; D048308:Mitogen-Activated Protein Kinase 14; D015843:Serpins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C497109:ATF4 protein, human; C585496:CYP1B1 protein, human