Associations between arsenic exposure and global posttranslational histone modifications among adults in Bangladesh.
BACKGROUND
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
Exposure to As is associated with alterations of global PTHMs; gender-specific patterns of association were observed between As exposure and several histone marks.


CONCLUSIONS
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.
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA.
Yana
Y
Chervona
Megan N
MN
Hall
Adriana
A
Arita
Fen
F
Wu
Hong
H
Sun
Hsiang-Chi
HC
Tseng
Eunus
E
Ali
Mohammad Nasir
MN
Uddin
Xinhua
X
Liu
Maria Antonietta
MA
Zoroddu
Mary V
MV
Gamble
Max
M
Costa
D000107:Acetylation / Q000187:drug effects; D000328:Adult; D001151:Arsenic / Q000032:analysis* / Q000652:urine; D020261:Arsenic Poisoning / Q000378:metabolism* / Q000652:urine; D001459:Bangladesh; D015331:Cohort Studies; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D006657:Histones / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008297:Male; D008745:Methylation / Q000187:drug effects; D010865:Pilot Projects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012737:Sex Factors
D006657:Histones; D001151:Arsenic