Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

• Published in: Toxicology and applied pharmacology Vol. 321; pp. 57 - 66
• Main Authors: Ameer, Syeda Shegufta, Engström, Karin, Hossain, Mohammad Bakhtiar, Concha, Gabriela, Vahter, Marie, Broberg, Karin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-04-2017
• Subjects: 60 APPLIED LIFE SCIENCES; Adolescent; Adult; ANDES; APOPTOSIS; Argentina - epidemiology; ARSENIC; Arsenic - administration & dosage; Arsenic - toxicity; Arsenic metabolism efficiency; Arsenic Poisoning - blood; Arsenic Poisoning - epidemiology; Arsenic Poisoning - genetics; Basic Medicine; BLOOD; Cancer; Child; CONCENTRATION RATIO; DNA; DNA Methylation - drug effects; DNA Methylation - physiology; DRINKING WATER; Drinking Water - adverse effects; Epigenetic; Farmakologi och toxikologi; Female; Gene Expression - drug effects; Gene Expression - physiology; GENES; Genome-wide; HEALTH HAZARDS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; Humans; HYDRIDES; ICP MASS SPECTROSCOPY; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; METABOLISM; METABOLITES; METHYLATION; Middle Aged; NEOPLASMS; Pathway analyses; Pharmacology and Toxicology; URINE; Young Adult; MMA; Arsenic metabolism efficiency; Pathway analyses; DMA; iAs; Genome-wide; ICP-MS; Epigenetic; U-As; Cancer
• ISSN: 0041-008X; 1096-0333; 1096-0333
• DOI: 10.1016/j.taap.2017.02.019

Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation.
To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism.
The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by the urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N=80 women) and DNA methylation (N=93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively.
U-As concentrations, ranging 10–1251μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes.
Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap.
•Women exposed to inorganic arsenic were studied for molecular responses in blood.•Arsenic is associated with decreased gene expression and increased DNA methylation.•Arsenic related pathways differed to some extent due to arsenic metabolism efficiency.