title: Global DNA methylation and low-level exposure to benzene.
abstract: BACKGROUND
  Global genomic hypomethylation is a common event in cancer tissues that is frequently observed in hematopoietic malignancies, including leukemia. Benzene, an established leukemogen at high doses, has been suggested to induce hypomethylation based on investigations of DNA methylation in LINE-1 and Alu repetitive elements. Whether global genomic DNA methylation content is reduced in response to benzene exposure is still undetermined.
  
  
  METHODS
  We measured global DNA methylation in 78 gasoline station attendants and 58 controls in peripheral blood cells using high-resolution gas chromatography-mass spectrometry. PCR-Pyrosequencing measures of DNA methylation at Alu and LINE-1 repetitive elements, representing a large proportion of methylation in non-coding regions, were also available. Exposure markers included personal airborne benzene, and urinary benzene, t,t-muconic acid (t,t-MA) and S-phelylmercapturic acid.
  
  
  RESULTS
  Mean global DNA methylation was 5.474 (+/- 0.083) %5mC in controls and 5.409 (+/- 0.142) %5mC in exposed participants (p = 0.01). All methylation markers were negatively correlated with airborne benzene. Alu and LINE-1 methylation, but not global DNA methylation, were negatively associated with t,t-MA; no association with the other urinary biomarkers was found. Multiple linear regression analysis adjusted for gender and age confirmed the results of correlation analysis and showed a 1.6% decrease in global DNA methylation associated with being gasoline station attendants. Alu and LINE-1 methylation levels were not associated with global DNA methylation.
  
  
  CONCLUSIONS
  Our results show that benzene exposure is associated with alterations in both global DNA and repetitive element methylation. Global and repetitive element methylation levels are not correlated in blood DNA, likely representing independent responses to benzene exposure.
authors.affiliation: Department of Occupational and Environmental Medicine, University of Milan and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. silvia.fustinoni@unimi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.forename: Federica
authors.initials: F
authors.lastname: Rossella
authors.forename: Elisa
authors.initials: E
authors.lastname: Polledri
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Laura
authors.initials: L
authors.lastname: Campo
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.forename: L
authors.initials: L
authors.lastname: Agnello
authors.forename: D
authors.initials: D
authors.lastname: Consonni
authors.forename: Angela C
authors.initials: AC
authors.lastname: Pesatori
authors.forename: A
authors.initials: A
authors.lastname: Baccarelli
authors.forename: P A
authors.initials: PA
authors.lastname: Bertazzi
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000032:analysis; D001554:Benzene / Q000009:adverse effects* / Q000032:analysis; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D023281:Genomics; D019337:Hematologic Neoplasms / Q000097:blood / Q000652:urine; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis; D008297:Male; D008432:Mathematical Computing; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D016133:Polymerase Chain Reaction; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D000395:Air Pollutants, Occupational; D015415:Biomarkers; D001554:Benzene