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; 312:139-147TL
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.