Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Exposure to arsenic via drinking water induces 5-hydroxymethylcytosine alteration in rat
AU - Zhang, Jie
AU - Mu, Xiaoli
AU - Xu, Weipan
AU - Martin, Francis Luke
AU - Alamdar, Ambreen
AU - Liu, Liangpo
AU - Tian, Meiping
AU - Huang, Qingyu
AU - Shen, Heqing
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Arsenic exposure has been implicated to alter DNA methylation process in vitro and in vivo, but it remains obscure whether it disrupts DNA demethylation process, which is pivotal for epigenetic regulation. The objective of this descriptive study was to investigate the relationship between arsenic exposure and 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) alterations in various organs. In this study, we exposed male Sprague–Dawley rats to sodium arsenite (0.5, 2 or 10 ppm) via drinking water for 8 weeks. Spleen accumulated 2- to 3-fold higher arsenic levels than liver and heart. Lower arsenic levels were observed in the kidney, pancreas and lung. No significant arsenic-induced global 5mC alterations were observed in the majority of investigated organs. However, arsenic induced organ-specific alterations of 5hmC and/or 5hmC/5mC in some investigated organs, i.e. lung, heart, kidney, pancreas and spleen. Our observations suggest that 5hmC is a more sensitive biomarker of arsenic-induced impacts on epigenetic processes than 5mC. Moreover, demethylation via hydroxylation of 5mC appears to play a central role in the toxic mechanism of arsenic.
AB - Arsenic exposure has been implicated to alter DNA methylation process in vitro and in vivo, but it remains obscure whether it disrupts DNA demethylation process, which is pivotal for epigenetic regulation. The objective of this descriptive study was to investigate the relationship between arsenic exposure and 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) alterations in various organs. In this study, we exposed male Sprague–Dawley rats to sodium arsenite (0.5, 2 or 10 ppm) via drinking water for 8 weeks. Spleen accumulated 2- to 3-fold higher arsenic levels than liver and heart. Lower arsenic levels were observed in the kidney, pancreas and lung. No significant arsenic-induced global 5mC alterations were observed in the majority of investigated organs. However, arsenic induced organ-specific alterations of 5hmC and/or 5hmC/5mC in some investigated organs, i.e. lung, heart, kidney, pancreas and spleen. Our observations suggest that 5hmC is a more sensitive biomarker of arsenic-induced impacts on epigenetic processes than 5mC. Moreover, demethylation via hydroxylation of 5mC appears to play a central role in the toxic mechanism of arsenic.
KW - Arsenic
KW - DNA methylation
KW - DNA demethylation
KW - 5-Hydroxymethylcytosine
KW - 5-Methylcytosine
KW - Organ specificity
U2 - 10.1016/j.scitotenv.2014.08.009
DO - 10.1016/j.scitotenv.2014.08.009
M3 - Journal article
VL - 497-498
SP - 618
EP - 625
JO - Science of the Total Environment
JF - Science of the Total Environment
SN - 0048-9697
ER -