title: 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers.
abstract: Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M1dG per 108normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where M1dG may reflect an additional potential mechanism of asbestos-induced toxicity.
authors.affiliation: Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy; Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.affiliation: Cancer Risk Factor Branch, Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Cellai
authors.affiliation: Cancer Risk Factor Branch, Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Armelle
authors.initials: A
authors.lastname: Munnia
authors.affiliation: Department of Internal Medicine, University of Genoa and IRCSS AOU San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ugolini
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; Occupational Medicine Unit, University of Pisa, Pisa, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cristaudo
authors.affiliation: Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Neri
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors.forename: Mirta
authors.initials: M
authors.lastname: Milić
authors.affiliation: Occupational Medicine Unit, University of Pisa, Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonotti
authors.affiliation: Department of Pharmaceutical Sciences in the Bouve College of Health Sciences, Barnett Institute, Northeastern University, Boston, MA, United States.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Giese
authors.affiliation: Cancer Risk Factor Branch, Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy. Electronic address: m.peluso@ispo.toscana.it.
authors.forename: Marco E M
authors.initials: ME
authors.lastname: Peluso
mesh_terms: D000368:Aged; D001194:Asbestos / Q000097:blood / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D018736:DNA Adducts / Q000097:blood*; D003849:Deoxyguanosine / Q000097:blood / Q000633:toxicity*; D004522:Educational Status; D006801:Humans; D007558:Italy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects; D011684:Purine Nucleosides / Q000097:blood / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking
chemical_list: C491625:3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido(1,2-alpha)purin-10(3H)-one; D015415:Biomarkers; D018736:DNA Adducts; D011684:Purine Nucleosides; D017382:Reactive Oxygen Species; D001194:Asbestos; D003849:Deoxyguanosine
keywords: Asbestos; M(1)dG adducts; Oxidative stress and lipid peroxidationn; Tobacco smoking