Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Cytotoxicity evaluation and mechanism of endocrine-disrupting chemicals by the embryoid body test

  • Jung, Eui-Man (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Yoo, Yeong-Min (East Coast Life Sciences Institute, College of Life Science, Gangneung-Wonju National University) ;
  • Lee, Jae-Hwan (Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University) ;
  • Jeung, Eui-Bae (Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University)
  • Received : 2022.01.20
  • Accepted : 2022.03.23
  • Published : 2022.10.15
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Abstract

Endocrine-disrupting chemicals (EDCs) are a structurally diverse class of synthetic and natural compounds. EDCs can cause non-communicable diseases such as obesity, type 2 diabetes, thyroid disorders, neurodevelopmental disease, hormone-dependent cancers, and reproductive disorders. The embryoid body test (EBT) is a developmental toxicity test method that determines the size of embryoid bodies (EBs) and the viability of mouse embryonic stem cells (mESCs) and fibroblasts (3T3 cells). The present study used the EBT to perform cytotoxicity evaluations of 10 EDCs and assessed the mechanistic relationship between endoplasmic reticulum (ER) stress and cytotoxicity. According to the statistical analysis and prediction model results, methylparaben, butylparaben, propylparaben, ethylparaben, triclosan, octylphenol, methoxychlor, bisphenol A, and diethylstilbestrol were classified as cytotoxic, but trichloroacetic acid was non-toxic. Classification accuracy was 90%. The mechanistic study showed that the cytotoxicities of butylparaben, propylparaben, octylphenol, and triclosan were induced by ER stress. The mRNA expressions of BiP, CHOP, and ATF4 were significantly higher following treatments with four EDCs compared to those after the control treatment. Compared to the control treatment, the mRNA levels of XBP1u and XBP1s increased significantly after butylparaben and propylparaben treatments, but did not increase with octylphenol and triclosan treatments. These results indicate that the EBT can be applied as an alternative toxicity test when evaluating the cytotoxicity of EDCs.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A2C2093275) and supported by Global Research and Development Center (GRDC) Program through the NRF funded by the Ministry of Education, Science and Technology (2017K1A4A3014959).

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