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

Abstract

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.

Global methylation profiles in DNA from different blood cell types

“…There is widespread interest in exploring the associations between WBC genomic m5C content and clinical outcomes, as well as environmental, lifestyle and dietary exposures. 26,27,39,40 Studies suggest that global DNA methylation levels decrease with time and thus a role for both endogenous and exogenous factors in changing global DNA methylation levels has been supported. 39 Although there are various methods for studying DNA methylation on a genome-wide scale, 41 2) in a 30 μL mixture and incubated for 1 h at 37°C.…”

Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults

“…Certain confounders (gender, age, cigarette smoking and water As) were selected a priori based on biologic plausibility and previous studies in the literature. 61 Other potential confounders (plasma folate, plasma Hcys, plasma vitamin B 12 , betel nut chewing, BMI, television ownership, education) were considered by examining their bivariate associations with blood GSH redox variables, blood SAM and […”

“…Genomic DNA methylation was measured using the [ 3 H]-methyl incorporation assay of Balaghi and Wagner, 60 as previously described. 61 The assay employs 3 H-labeled SAM and SssI methylase to add 3 H-labeled methyl groups to unmethylated CpG sequences. Thus, the DPM values are inversely related to global DNA methylation.…”

DNA methylation in white blood cells

“…Using the methyl acceptor assay, an unexpected dose-dependent hypermethylation of WBC DNA was found in Bangladeshi adults with chronic arsenic exposure. 35 This effect was modified by folate, suggesting that arsenic-induced increases in DNA methylation were dependent upon methyl availability. Arsenic has been associated with gene-specific hypermethylation of p53 and p16 promoter regions in blood DNA of subjects exposed to toxic level of arsenic compared to controls.…”

“…35 Studies have correlated age with two of the repetitive elements, LINE-1 and Alu. Although one study correlated lower levels of LINE-1 with increasing age, 36 most of the studies did not find an agedependent effect on blood LINE-1 methylation.…”