Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

Molly L. Kile, Andrea Baccarelli, Elaine Hoffman, Letizia Tarantini, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mahiuddin, Golam Mostofa, Yu Mei Hsueh, Robert O. Wright, David C. Christiani

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99 引文 斯高帕斯(Scopus)

摘要

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: 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.

原文英語
頁(從 - 到)1061-1066
頁數6
期刊Environmental Health Perspectives
120
發行號7
DOIs
出版狀態已發佈 - 六月 2012

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

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    Kile, M. L., Baccarelli, A., Hoffman, E., Tarantini, L., Quamruzzaman, Q., Rahman, M., Mahiuddin, G., Mostofa, G., Hsueh, Y. M., Wright, R. O., & Christiani, D. C. (2012). Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. Environmental Health Perspectives, 120(7), 1061-1066. https://doi.org/10.1289/ehp.1104173