TY - JOUR
T1 - The embryonic toxicity evaluation of deoxynivalenol (DON) by murine embryonic stem cell test and human embryonic stem cell test models
AU - Fang, Haiqin
AU - Zhi, Yuan
AU - Yu, Zhou
AU - Lynch, Robert A.
AU - Jia, Xudong
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/4
Y1 - 2018/4
N2 - Deoxynivalenol (DON) is a group B trichothecene and a common contaminant of food crops worldwide. DON is known to cause a spectrum of diseases in animals and humans such as vomiting and gastroenteritis and has been shown to cross the human placental barrier; therefore, dietary exposure during pregnancy could lead to exposure of the fetus. Since the mechanism of DON toxicity action has not been thoroughly elucidated, further evaluation of the underlying mechanisms of DON's embryotoxicity is needed. This is especially important for developing exposure guidance recommendations, especially those targeted towards pregnant women. In the present study, murine embryonic stem cell test (mEST) and human embryonic stem cell test (hEST) models were developed according to protocols of the European Centre for the Validation of Alternative Methods (ECVAM). Different concentrations of DON were administered to mouse embryonic stem cells D3 (mESC-D3), mouse Balb/c-3T3 (3T3) embryo fibroblast cells, and human embryonic stem cells H9 (hESC-H9) for 10 days to detect the 50% inhibitory proliferation concentration (IC50) of mESC-D3 cells, 3T3 cells, and hESC-H9 cells with DON. Differentiation of ESCs was initiated by embryoid body (EBs) formation. EBs were exposed to different concentrations of DONfor 10 days. The expression of cardiomyocyte differentiation gene alpha-myosin heavy chain (α-MHC) was detected by real-time PCR and the 50% inhibition of cardiomyocyte differentiation (ID50) was determined. Based on the values of IC50 and ID50, functions I, II, and III were calculated by three linear discriminant functions in the EST model and the embryotoxicity of DON was described by comparing the three functions. Results of the three endpoints of DON in murine EST were 0.141 μg/ml (IC50 3T3), 0.085 μg/ml (IC50 D3), and 0.110 μg/ml (ID50 D3). The function I (−34.43), function Ⅱ (−18.62), and function III (1.98) were calculated for DON by themEST model. The three endpoints of DON in hEST were 0.13 μg/ml (IC50 3T3), 0.11 μg/ml (IC50 H9), and 0.078 μg/ml (ID50). Function I (−25.97), function Ⅱ (−13.18), and function III (−0.12) were calculated based on IC50 and ID50. Since function III > function II > function I, according to the EST criteria, DON was determined to have strong embryo toxicity both by mEST and hEST. Moreover, the hEST model, which excluded species differences, is suggested to be a more accurate and reliable method for the evaluation of chemical embryotoxicity.
AB - Deoxynivalenol (DON) is a group B trichothecene and a common contaminant of food crops worldwide. DON is known to cause a spectrum of diseases in animals and humans such as vomiting and gastroenteritis and has been shown to cross the human placental barrier; therefore, dietary exposure during pregnancy could lead to exposure of the fetus. Since the mechanism of DON toxicity action has not been thoroughly elucidated, further evaluation of the underlying mechanisms of DON's embryotoxicity is needed. This is especially important for developing exposure guidance recommendations, especially those targeted towards pregnant women. In the present study, murine embryonic stem cell test (mEST) and human embryonic stem cell test (hEST) models were developed according to protocols of the European Centre for the Validation of Alternative Methods (ECVAM). Different concentrations of DON were administered to mouse embryonic stem cells D3 (mESC-D3), mouse Balb/c-3T3 (3T3) embryo fibroblast cells, and human embryonic stem cells H9 (hESC-H9) for 10 days to detect the 50% inhibitory proliferation concentration (IC50) of mESC-D3 cells, 3T3 cells, and hESC-H9 cells with DON. Differentiation of ESCs was initiated by embryoid body (EBs) formation. EBs were exposed to different concentrations of DONfor 10 days. The expression of cardiomyocyte differentiation gene alpha-myosin heavy chain (α-MHC) was detected by real-time PCR and the 50% inhibition of cardiomyocyte differentiation (ID50) was determined. Based on the values of IC50 and ID50, functions I, II, and III were calculated by three linear discriminant functions in the EST model and the embryotoxicity of DON was described by comparing the three functions. Results of the three endpoints of DON in murine EST were 0.141 μg/ml (IC50 3T3), 0.085 μg/ml (IC50 D3), and 0.110 μg/ml (ID50 D3). The function I (−34.43), function Ⅱ (−18.62), and function III (1.98) were calculated for DON by themEST model. The three endpoints of DON in hEST were 0.13 μg/ml (IC50 3T3), 0.11 μg/ml (IC50 H9), and 0.078 μg/ml (ID50). Function I (−25.97), function Ⅱ (−13.18), and function III (−0.12) were calculated based on IC50 and ID50. Since function III > function II > function I, according to the EST criteria, DON was determined to have strong embryo toxicity both by mEST and hEST. Moreover, the hEST model, which excluded species differences, is suggested to be a more accurate and reliable method for the evaluation of chemical embryotoxicity.
KW - Deoxynivalenol (DON)
KW - Embryonic stem cell test (mEST)
KW - Embryotoxicity
KW - Human embryonic stem cell test (hEST)
UR - http://www.scopus.com/inward/record.url?scp=85042172822&partnerID=8YFLogxK
U2 - 10.1016/j.foodcont.2017.10.018
DO - 10.1016/j.foodcont.2017.10.018
M3 - Article
AN - SCOPUS:85042172822
SN - 0956-7135
VL - 86
SP - 234
EP - 240
JO - Food Control
JF - Food Control
ER -
