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

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Ameer, Syeda SheguftaLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine (author)

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

Article/chapterEnglish2017

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Elsevier BV,2017
10 s.

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LIBRIS-ID:oai:lup.lub.lu.se:f4236cad-dcc6-4f93-80e1-c4fe777c4513
https://lup.lub.lu.se/record/f4236cad-dcc6-4f93-80e1-c4fe777c4513URI
https://doi.org/10.1016/j.taap.2017.02.019DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:135604652URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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Background 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. Objectives To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods 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. Results U-As concentrations, ranging 10–1251 μg/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 1000 CpGs 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. Conclusions Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
Arsenic metabolism efficiency
Cancer
Epigenetic
Genome-wide
Pathway analyses

Added entries (persons, corporate bodies, meetings, titles ...)

Engström, KarinKarolinska Institute,Lund University,Lunds universitet,Genetisk arbets- och miljömedicin,Forskargrupper vid Lunds universitet,Genetic Occupational and Environmental Medicine,Lund University Research Groups(Swepub:lu)med-ksk (author)
Hossain, BakhtiarLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-bkh (author)
Concha, GabrielaNational Food Agency (author)
Vahter, MarieKarolinska Institutet,Karolinska Institute (author)
Broberg, KarinKarolinska Institutet,Karolinska Institute(Swepub:lu)kgen-kbr (author)
Avdelningen för arbets- och miljömedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

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In:Toxicology and Applied Pharmacology: Elsevier BV321, s. 57-660041-008X1096-0333

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