Associations of Plasma Selenium with Arsenic and Genomic Methylation of Leukocyte DNA in Bangladesh

Pilsner JR, Hall MN, Liu X, Ahsan H, Ilievski V, Slavkovich V, Levy D, Factor-Litvak P, Graziano JH, Gamble

MV. Environ Health Perspect. 2010 Sep 15. PMID: 20843762  

Background: Global hypomethylation of DNA is thought to constitute an early event in some cancers and occurs in response to arsenic (As) exposure and/or selenium (Se) deficiency in in vitro and in animal models. In addition, antagonism between As and Se whereby each reduces toxicity of the other has been well documented in animal models. Selenium status may therefore modify the health effects of As in As-exposed populations.

Objective: The primary study objectives were to test the hypothesis that selenium deficiency is associated with genomic hypomethylation of lymphocyte DNA, and to determine whether Se levels are associated with blood and urinary As concentrations in adults exposed to As contaminated groundwater in Bangladesh. A secondary objective was to explore the relationships between plasma Se and As metabolites.

Design: We assessed plasma Se concentrations, As metabolite profiles in blood and urine, and genomic methylation of leukocyte DNA in a cross-sectional study of 287 adults.

Results: After adjustment for potential confounders, we observed an inverse association between Se (µg/L) and genomic DNA methylation (b=345.6, 95% CI (confidence interval), 59 - 632 DPM/ug DNA for a 1 µg/L increase in Se). Se concentrations were inversely associated with total As concentrations (µg/L) in blood (b=-0.04, 95% CI,-0.08 to -0.01) and urine (β=-20.1, 95% CI, -29.3 to -10.9). Selenium levels were negatively associated with %MMA (b=-0.59, 95% CI, -1.04 to -0.13) and positively associated with %DMA (b=0.53, 95% CI, 0.04 to 1.01) in blood.

Conclusions: The results suggest that Se is inversely associated with genomic DNA methylation. The underlying mechanisms and implications of this observation are unclear and warrant further investigation. In addition, Se may influence blood and urinary As concentrations, as well as relative proportions of As metabolites in blood.