Title: Associations between arsenic exposure and global posttranslational histone modifications among adults in Bangladesh.
Authors: Chervona, Yana; Hall, Megan N; Arita, Adriana; Wu, Fen; Sun, Hong; Tseng, Hsiang-Chi; Ali, Eunus; Uddin, Mohammad Nasir; Liu, Xinhua; Zoroddu, Maria Antonietta; Gamble, Mary V; Costa, Max
Published In Cancer Epidemiol Biomarkers Prev, (2012 Dec)
Abstract: Exposure to arsenic (As) is associated with an increased risk of several cancers as well as cardiovascular disease, and childhood neuro-developmental deficits. Arsenic compounds are weakly mutagenic, alter gene expression and posttranslational histone modifications (PTHMs) in vitro.Water and urinary As concentrations as well as global levels of histone 3 lysine 9 di-methylation and acetylation (H3K9me2 and H3K9ac), histone 3 lysine 27 tri-methylation and acetylation (H3K27me3 and H3K27ac), histone 3 lysine 18 acetylation (H3K18ac), and histone 3 lysine 4 trimethylation (H3K4me3) were measured in peripheral blood mononuclear cells (PBMC) from a subset of participants (N = 40) of a folate clinical trial in Bangladesh (FACT study).Total urinary As (uAs) was positively correlated with H3K9me2 (r = 0.36, P = 0.02) and inversely with H3K9ac (r = -0.47, P = 0.002). The associations between As and other PTHMs differed in a gender-dependent manner. Water As (wAs) was positively correlated with H3K4me3 (r = 0.45, P = 0.05) and H3K27me3 (r = 0.50, P = 0.03) among females and negatively correlated among males (H3K4me3: r = -0.44, P = 0.05; H3K27me3: r = -0.34, P = 0.14). Conversely, wAs was inversely associated with H3K27ac among females (r = -0.44, P = 0.05) and positively associated among males (r = 0.29, P = 0.21). A similar pattern was observed for H3K18ac (females: r = -0.22, P = 0.36; males: r = 0.27, P = 0.24).Exposure to As is associated with alterations of global PTHMs; gender-specific patterns of association were observed between As exposure and several histone marks.These findings contribute to the growing body of evidence linking As exposure to epigenetic dysregulation, which may play a role in the pathogenesis of As toxicity.
PubMed ID: 23064002
MeSH Terms: Acetylation/drug effects; Adult; Arsenic Poisoning/metabolism*; Arsenic Poisoning/urine; Arsenic/analysis*; Arsenic/urine; Bangladesh; Cohort Studies; Environmental Exposure/analysis*; Female; Histones/metabolism*; Histones/urine; Humans; Male; Methylation/drug effects; Pilot Projects; Protein Processing, Post-Translational/drug effects*; Sex Factors