title: Tetrachloro-1,4-benzoquinone induces apoptosis of mouse embryonic stem cells.
abstract: Pentachlorophenol (PCP) is a widespread, persistent environmental contaminant, and it is enzymatically activated to form a reactive metabolite, tetrachloro-1,4-benzoquinone (TCBQ). To our knowledge, there is no information about TCBQ toxicity on embryonic stem cells. Here, we demonstrated that TCBQ induced significantly apoptosis of mouse embryonic stem cells in a concentration-dependent manner. We also showed that TCBQ elevated genomic 5-hydroxymethylcytosine (5hmC) by affecting ten-eleven translocation (Tet) dioxygenases in mouse embryonic stem cells. We further investigated whether Tet dioxygenases were implicated in TCBQ-induced apoptosis. By depleting all three dioxygenases (Tet1-3), we found that Tet dioxygenases slightly inhibited both early and late apoptosis induced by TCBQ at a low concentration (30μmol/L). Meanwhile, treated by TCBQ at higher concentrations (40 and 50μmol/L), the total percentage of apoptotic cells was not affected by Tet dioxygenases. However, Tet dioxygenases tended to arrest mouse ES cells to be at early apoptotic stage and to reduce the cells to enter later apoptotic stage. These results indicate that Tet dioxygenases play a role in shaping TCBQ-induced apoptosis in mouse embryonic stem cells. Our study provides new insights into the toxicology of PCP and its reactive metabolite TCBQ.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: licuiping198585@126.com.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Fengbang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: hlwang@rcees.ac.cn.
authors.forename: Hailin
authors.initials: H
authors.lastname: Wang
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D017209:Apoptosis; D002703:Chloranil / Q000633:toxicity*; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells; D018675:Toxicity Tests
chemical_list: D005659:Fungicides, Industrial; D002703:Chloranil; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5-Hydroxymethylcytosine; Early apoptosis; Late apoptosis; Ten-eleven translocation; Tetrachloro-1,4-benzoquinone