title: Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes.
abstract: BACKGROUND
  Arsenic is an epigenetic toxicant and could influence fetal developmental programming.
  
  
  OBJECTIVE
  We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.
  
  
  METHODS
  Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.
  
  
  RESULTS
  Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1-230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.
  
  
  CONCLUSIONS
  Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.
authors.affiliation: Oregon State University, College of Public Health and Human Sciences, Corvallis, Oregon 97331, USA. molly.kile@oregonstate.edu
authors.forename: Molly L
authors.initials: ML
authors.lastname: Kile
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Elaine
authors.initials: E
authors.lastname: Hoffman
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Quazi
authors.initials: Q
authors.lastname: Quamruzzaman
authors.forename: Mahmuder
authors.initials: M
authors.lastname: Rahman
authors.forename: Golam
authors.initials: G
authors.lastname: Mahiuddin
authors.forename: Golam
authors.initials: G
authors.lastname: Mostofa
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D001151:Arsenic