title: A dose-response study of arsenic exposure and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults.
abstract: BACKGROUND
  Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation.
  
  
  OBJECTIVE
  The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water.
  
  
  METHODS
  Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [3H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation.
  
  
  RESULTS
  Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-μg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures.
  
  
  CONCLUSIONS
  These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Niedzwiecki
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.forename: Julie
authors.initials: J
authors.lastname: Oka
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Harper
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.forename: Alexander
authors.initials: A
authors.lastname: van Geen
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Mey
authors.forename: Shafiul
authors.initials: S
authors.lastname: Alam
authors.forename: Abu B
authors.initials: AB
authors.lastname: Siddique
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D000328:Adult; D001151:Arsenic / Q000097:blood / Q000633:toxicity* / Q000652:urine; D001459:Bangladesh; D002851:Chromatography, High Pressure Liquid; D003124:Colorimetry; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000009:adverse effects / Q000737:chemistry*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012436:S-Adenosylmethionine / Q000097:blood; D018709:Statistics, Nonparametric; D014316:Tritium; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; D006710:Homocysteine; D014316:Tritium; D012436:S-Adenosylmethionine; D005492:Folic Acid; D001151:Arsenic