HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pilsner, J R. Articles by Gamble, M. V Search for Related Content PubMed PubMed Citation Articles by Pilsner, J R. Articles by Gamble, M. V Agricola Articles by Pilsner, J R. Articles by Gamble, M. V

Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults^1,2,3

¹ From the Departments of Environmental Health Sciences (JRP, VI, VS, JHG, and MVG), Biostatistics (XL and DL), and Epidemiology (HA and PF-L), Mailman School of Public Health; and the Department of Pharmacology (JHG), College of Physicians and Surgeons, Columbia University, New York, NY

Background: Studies in cell culture and animal models indicate that arsenic exposure induces modifications in DNA methylation, including genome-wide DNA hypomethylation. It is not known whether arsenic exposure influences genomic DNA methylation in human populations chronically exposed to arsenic-contaminated drinking water.

Objective: The objective of this study was to determine whether arsenic is associated with genomic hypomethylation of peripheral blood leukocyte (PBL) DNA in Bangladeshi adults who are chronically exposed to arsenic. We also investigated whether arsenic-induced alterations in DNA methylation may be influenced by folate nutritional status.

Design: PBL DNA methylation and concentrations of plasma folate, plasma arsenic, and urinary arsenic were assessed in 294 adults in Araihazar, Bangladesh. Genomic PBL DNA methylation was measured by using a [³H]-methyl incorporation assay.

Results: Urinary arsenic, plasma arsenic, and plasma folate were positively associated with the methylation of PBL DNA (P = 0.009, 0.03, and 0.03, respectively). Stratification of participants by folate nutritional status [<9 nmol/L (n = 190) or 9 nmol/L (n = 104)] showed that the associations between arsenic exposure and methylation of PBL DNA were restricted to persons with folate concentrations 9 nmol/L.

Conclusions: Contrary to our a priori hypothesis, arsenic exposure was positively associated with genomic PBL DNA methylation in a dose-dependent manner. This effect is modified by folate, which suggests that arsenic-induced increases in DNA methylation cannot occur in the absence of adequate folate. The underlying mechanisms and physiologic implications of increased genomic DNA methylation are unclear, and they warrant further study.

Key Words: DNA methylation • epigenetics • folate • folic acid • folate deficiency • one-carbon metabolism • S-adenosylmethionine • SAM • arsenic • arsenicosis • Bangladesh • well water

This article has been cited by other articles:

				M. B. Terry, J. S. Ferris, R. Pilsner, J. D. Flom, P. Tehranifar, R. M. Santella, M. V. Gamble, and E. Susser Genomic DNA Methylation among Women in a Multiethnic New York City Birth Cohort Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2306 - 2310. [Abstract] [Full Text] [PDF]