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Assessment of the carcinogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin using mouse embryonic stem cells to form teratoma in vivo.

Abstract

As the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has gained lots of concerns, due to its diverse deleterious effects. However, the knowledge on carcinogenic risk of TCDD during early stage of development remains scarce. The in vivo teratoma formation model based on the transplantation of embryonic stem cells (ESCs) in immunodeficient mice is appealing for studying pluripotency and tumorigenicity in developmental biology, and also shows promise in environmental toxicology, especially in carcinogenesis researches. In this study, the malignant transformation of mouse embryonic stem cells (mESCs) pretreated with TCDD was investigated during their in vivo differentiation using teratoma formation model. Based on characterization of the pluripotency and differentiation capabilities of mESCs, evil changes in teratomas derived from TCDD-exposed mESCs were systematically studied. The results showed that TCDD significantly up-regulated CYP1A1 transcriptional levels in mESCs, elevated the incidence of malignant change in mESC-derived teratomas, and caused indefinite proliferation capabilities in sequential cultures of tumor tissues. The findings suggested that TCDD could exert carcinogenic effect on mESCs during their differentiation into teratoma in vivo, and more attention should be paid to the adverse health effects of this chemical during gestation or early developmental period.

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  • Authors+Show Affiliations

    ,

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.

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    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, 030006, China.

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    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.

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    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

    ,

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

    ,

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China; Institute of Environment and Health, Jianghan University, Wuhan, 430056, China. Electronic address: zhouqf@rcees.ac.cn.

    ,

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: faiola@rcees.ac.cn.

    ,

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.

    Source

    Toxicology letters 312: 2019 May 10 pg 139-147

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31082521

    Citation

    Yang, Xiaoxi, et al. "Assessment of the Carcinogenic Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin Using Mouse Embryonic Stem Cells to Form Teratoma in Vivo." Toxicology Letters, vol. 312, 2019, pp. 139-147.
    Yang X, Ku T, Sun Z, et al. Assessment of the carcinogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin using mouse embryonic stem cells to form teratoma in vivo. Toxicol Lett. 2019;312:139-147.
    Yang, X., Ku, T., Sun, Z., Liu, Q. S., Yin, N., Zhou, Q., ... Jiang, G. (2019). Assessment of the carcinogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin using mouse embryonic stem cells to form teratoma in vivo. Toxicology Letters, 312, pp. 139-147. doi:10.1016/j.toxlet.2019.05.012.
    Yang X, et al. Assessment of the Carcinogenic Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin Using Mouse Embryonic Stem Cells to Form Teratoma in Vivo. Toxicol Lett. 2019 May 10;312:139-147. PubMed PMID: 31082521.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Assessment of the carcinogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin using mouse embryonic stem cells to form teratoma in vivo. AU - Yang,Xiaoxi, AU - Ku,Tingting, AU - Sun,Zhendong, AU - Liu,Qian S, AU - Yin,Nuoya, AU - Zhou,Qunfang, AU - Faiola,Francesco, AU - Liao,Chunyang, AU - Jiang,Guibin, Y1 - 2019/05/10/ PY - 2018/09/10/received PY - 2019/03/21/revised PY - 2019/05/09/accepted PY - 2019/5/15/pubmed PY - 2019/5/15/medline PY - 2019/5/15/entrez KW - Carcinogenic effects KW - Mouse embryonic stem cells KW - TCDD KW - Teratocarcinoma KW - Teratoma formation SP - 139 EP - 147 JF - Toxicology letters JO - Toxicol. Lett. VL - 312 N2 - As the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has gained lots of concerns, due to its diverse deleterious effects. However, the knowledge on carcinogenic risk of TCDD during early stage of development remains scarce. The in vivo teratoma formation model based on the transplantation of embryonic stem cells (ESCs) in immunodeficient mice is appealing for studying pluripotency and tumorigenicity in developmental biology, and also shows promise in environmental toxicology, especially in carcinogenesis researches. In this study, the malignant transformation of mouse embryonic stem cells (mESCs) pretreated with TCDD was investigated during their in vivo differentiation using teratoma formation model. Based on characterization of the pluripotency and differentiation capabilities of mESCs, evil changes in teratomas derived from TCDD-exposed mESCs were systematically studied. The results showed that TCDD significantly up-regulated CYP1A1 transcriptional levels in mESCs, elevated the incidence of malignant change in mESC-derived teratomas, and caused indefinite proliferation capabilities in sequential cultures of tumor tissues. The findings suggested that TCDD could exert carcinogenic effect on mESCs during their differentiation into teratoma in vivo, and more attention should be paid to the adverse health effects of this chemical during gestation or early developmental period. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/31082521/Assessment_of_the_carcinogenic_effect_of_2,3,7,8-tetrachlorodibenzo-p-dioxin_using_mouse_embryonic_stem_cells_to_form_teratoma_in_vivo L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(18)31885-X DB - PRIME DP - Unbound Medicine ER -