摘要
Pentachlorophenol（PCP） is a widespread,persistent environmental contaminant,and it is enzymatically activated to form a reactive metabolite,tetrachloro-l,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 genomic5-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（30 μmol/L）.Meanwhile,treated by TCBQ at higher concentrations（40and 50 μmol/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.
Pentachlorophenol（PCP） is a widespread,persistent environmental contaminant,and it is enzymatically activated to form a reactive metabolite,tetrachloro-l,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 genomic5-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（30 μmol/L）.Meanwhile,treated by TCBQ at higher concentrations（40and 50 μmol/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.
基金
supported by the National Natural Science Foundation of China(Nos.21327006,21435008,21321004)
the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB14030200)
