Table 2.

Recent studies examining the relationship between histone PTMs and arsenic exposure

Type of study (in vitro, in vivo, human subjects)	Arsenical exposure	Cell type analyzed	Type of histone PTM analysis and method used	Major findings	Reference
Male steel workers from Italy (n = 63)	Cumulative exposure estimated by product of arsenic content in particulate matter (PM) in air and years of employment	PBLs	Global analysis of H3K4me2 and H3K9Ac levels determined using the sandwich enzyme-linked immunosorbent assay (ELISA).	Positive association between global H3K4me2 and H3K9Ac levels with cumulative arsenic exposure.	Cantone et al., 2011 [63]
Men (n = 20) and women (n = 20) from Bangladesh	Maternal U-tAs median = 247.8 μg/g creatinine	PBMCs	Global levels of various histone PTMs determined using the sandwich enzyme-linked immunosorbent assay (ELISA).	Positive associations between U-tAs and global H3K9me2 levels and negative associations between U-tAs and global H3K9ac levels across all individuals. Additional sex-specific associations between particular histone PTMs and U-tAs identified.	Chervona et al., 2012 [64•]
In vivo (mice) exposure to arsenite	50 ppm NaAsO2 in drinking water for six months	Whole liver of male C57Bl/6 J mice	Analysis of various histone PTMs within the promoter region of p16 gene using the chromatin immunoprecipitation (ChIP) assay. For p16 promoter, determined DNA methylation using bisulfite conversion of DNA, followed by PCR amplification and sequencing of cloned PCR products.	Downregulation of p16 mRNA, accompanied by increase in the transcription-restrictive modification H3K9me2 in p16 promoter but no change in p16 promoter DNA methylation status.	Suzuki et al., 2013 [65•]

HPLC-MS/MS: high-performance liquid chromatography tandem mass spectrometry

PBLs: peripheral blood lymphocytes

PBMCs: peripheral blood mononuclear cells

PCR: polymerase chain reaction

ND: non-detectable

U-tAs: total urinary arsenic (sum of iAs, MMAs, DMAs)