3,4-ジニトロフラザンフロキサンの胚発生毒性に関する胚性幹細胞テストモデルを用いた評価

Objective: To evaluate the potential embryonic developmental toxicity of 3, 4-dinitrofurazanfuroxan (DNTF) using embryonic stem cell test (EST) . Methods: In March 2024, the inhibitory effect of DNTF at different concentrations (0, 15.625, 31.250, 62.500, 125.000, 250.000, 500.000, and 1 000.000 μg/ml) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes, as well as its cytotoxicity to mESCs and 3T3 cells was detected. The known strong embryotoxic drug 5-fluorouracil (5-FU) and non-embryotoxic drug Penicillin-G (P-G) were used to validate the model effectiveness, and the embryotoxicity of DNTF was evaluated. Results: DNTF at concentrations of 31.250 μg/ml and above exhibited an inhibitory effect on mESC differentiation. The proliferation inhibition rates of mESCs and 3T3 cells in the DNTF groups at concentrations of 31.250, 62.500, 125.000, 250.000, 500.000, and 1 000.000 μg/ml were significantly higher than those in the control group (P<0.05). The half-maximal inhibitory concentration (IC(50)) of DNTF for mESC proliferation and differentiation were 633.91 μg/ml and 618.20 μg/ml, respectively. While the IC(50) for 3T3 cell proliferation was 700.84 μg/ml. Based on the validity verification with 5-FU and P-G, DNTF was determined to have no embryonic development toxicity. Conclusion: The EST model indicates that DNTF does not possess embryonic developmental toxicity.