title: Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length.
abstract: Studies of the effects of smoking on leukocyte telomere length (LTL) using cigarettes smoked per day or pack years smoked (PYS) present limitations. Reported high levels of smoking may not increase toxin exposure levels proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff volume and overall exposure based on total N-nitrosamines, is highly reproducible and independent of time since the last cigarette. We hypothesized that smokers with higher NMRs will exhibit increased total puff volume, reflecting efforts to extract more nicotine from their cigarettes and increasing toxin exposure. In addition, higher levels of smoking could cause a gross damage in LTL. The urinary cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood samples. We found a significant association between NMR and CYP2A6 genotype. Reduction in LTL was seen in relation to accumulated tobacco consumption and years smoking when we adjusted for age and gender. However, there were no significant differences between NMR values and LTL. In our study the higher exposure was associated with lower number of PYS. Smokers with reduced cigarette consumption may exhibit compensatory smoking behavior that results in no reduced tobacco toxin exposure. Our results suggest that lifetime accumulated smoking exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless, a combination of smoking topography (NMR) and consumption (PYS) measures may provide useful information about smoking effects on health outcomes.
authors.affiliation: Department of Morphological Sciences and Biomedicine, Universidad Europea, Madrid, Spain. Electronic address: zoraida.verde@uem.es.
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Verde
authors.affiliation: Department of Morphological Sciences and Biomedicine, Universidad Europea, Madrid, Spain; Occupational Medicine, Grupo Banco Popular, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Reinoso-Barbero
authors.affiliation: Department of Morphological Sciences and Biomedicine, Universidad Europea, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Chicharro
authors.affiliation: Faculty of Health and Sport Sciences, Universidad de Zaragoza, Huesca, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Garatachea
authors.affiliation: Department of Neumology, Hospital Guadalajara, Guadalajara, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Resano
authors.affiliation: Department of Neumology, Hospital Carlos III, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sánchez-Hernández
authors.affiliation: Department of Neumology, Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Rodríguez González-Moro
authors.affiliation: Department of Toxicology and Health Sanitary, Universidad Complutense, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bandrés
authors.affiliation: School of Doctoral Studies & Research, Universidad Europea, Madrid, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.affiliation: School of Doctoral Studies & Research, Universidad Europea, Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
mesh_terms: D015415:Biomarkers / Q000652:urine; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000648:ultrastructure*; D009538:Nicotine / Q000378:metabolism*; D012907:Smoking; D016615:Telomere; D014026:Nicotiana
chemical_list: D015415:Biomarkers; D009538:Nicotine; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6
keywords: 3-OH-cotinine; CYP2A6; Cotinine; Leukocyte telomere length; NMR; Nicotine; Pack years smoked