title: Exposure to arsenic via drinking water induces 5-hydroxymethylcytosine alteration in rat.
abstract: 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.
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China. Electronic address: jzhang@iue.ac.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Mu
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
authors.forename: Weipan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Martin
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
authors.forename: Ambreen
authors.initials: A
authors.lastname: Alamdar
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
authors.forename: Liangpo
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Tian
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China. Electronic address: hqshen@iue.ac.cn.
authors.forename: Heqing
authors.initials: H
authors.lastname: Shen
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D060766:Drinking Water; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D001151:Arsenic
keywords: 5-Hydroxymethylcytosine; 5-Methylcytosine; Arsenic; DNA demethylation; DNA methylation; Organ specificity