Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults.
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.


METHODS
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 [(3)H]-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 >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 >or= 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.
Pilsner
J Richard
JR
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 60 Haven Avenue, B1, New York, NY 10032, USA.
Liu
Xinhua
X
Ahsan
Habibul
H
Ilievski
Vesna
V
Slavkovich
Vesna
V
Levy
Diane
D
Factor-Litvak
Pam
P
Graziano
Joseph H
JH
Gamble
Mary V
MV
D000293:Adolescent; D000328:Adult; D000368:Aged; D001151:Arsenic / Q000097:blood* / Q000494:pharmacology*; D001459:Bangladesh; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011446:Prospective Studies; D014316:Tritium; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000009:adverse effects*
D014874:Water Pollutants, Chemical; D014316:Tritium; D014803:Vitamin B Complex; D005492:Folic Acid; D001151:Arsenic