IMR Press / FBL / Volume 28 / Issue 3 / DOI: 10.31083/j.fbl2803048
Open Access Original Research
Investigating Endocrine Disrupting Impacts of Nine Disinfection Byproducts on Human and Zebrafish Estrogen Receptor Alpha
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1 Korea Institute of Science and Technology Europe (KIST Europe) Forschungsgesellschaft GmbH, Joint Laboratory of Applied Ecotoxicology, Environmental Safety Group, Universität des Saarlandes, 66123 Saarbrücken, Germany
2 Office of Islands and Coastal Biology Research, Honam National Institute of Biological Resources (HNIBR), 58762 Mokpo, Republic of Korea
3 Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 15140 Lahti, Finland
4 Clayton H. Riddell Faculty of Environment, Earth, and Resources, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
5 Next&Bio Inc., 02841 Seoul, Republic of Korea
*Correspondence: (Young Jun Kim)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(3), 48;
Submitted: 26 December 2022 | Revised: 25 February 2023 | Accepted: 1 March 2023 | Published: 13 March 2023
(This article belongs to the Special Issue Role of Zebrafish in Human Disease Research)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Disinfection byproducts (DBPs) cause endocrine disruption via estrogenic or anti-estrogenic effects on estrogen receptors. However, most studies have focused on human systems, with little experimental data being presented on aquatic biota. This study aimed to compare the effects of nine DBPs on zebrafish and human estrogen receptor alpha (zERα and hERα). Methods: In vitro enzyme response-based tests, including cytotoxicity and reporter gene assays, were performed. Additionally, statistical analysis and molecular docking studies were employed to compare ERα responses. Results: Iodoacetic acid (IAA), chloroacetonitrile (CAN), and bromoacetonitrile (BAN) showed robust estrogenic activity on hERα(maximal induction ratios of 108.7%, 50.3%, and 54.7%, respectively), while IAA strongly inhibited the estrogenic activity induced by 17β-estradiol (E2) in zERα (59.8% induction at the maximum concentration). Chloroacetamide (CAM) and bromoacetamide (BAM) also showed robust anti-estrogen effects in zERα (48.1% and 50.8% induction at the maximum concentration, respectively). These dissimilar endocrine disruption patterns were thoroughly assessed using Pearson correlation and distance-based analyses. Clear differences between the estrogenic responses of the two ERαs were observed, whereas no pattern of anti-estrogenic activities could be established. Some DBPs strongly induced estrogenic endocrine disruption as agonists of hERα, while others inhibited estrogenic activity as antagonists of zERα. Principal coordinate analysis (PCoA) showed similar correlation coefficients for estrogenic and anti-estrogenic responses. Reproducible results were obtained from computational analysis and the reporter gene assay. Conclusions: Overall, the effects of DBPs on both human and zebrafish highlight the importance of controlling their differences in responsiveness for estrogenic activities including the water quality monitoring and endocrine disruption, as DBPs have species-specific ligand-receptor interactions.

disinfection byproduct
iodoacetic acid (IAA)
chloroacetonitrile (CAN)
bromoacetonitrile (BAN)
estrogenic effects

Cross-species-analysis of disinfection byproduct (DBP) effects is crucial for risk assessment
In vitro experiments explored endocrine disruption by DBPs between human and zebrafish
IAA, CAN, and BAN had robust estrogenic effects on human estrogen receptor α
IAA, CAM, and BAM had robust anti-estrogenic effects on zebrafish estrogen receptor α 
This study demonstrated differences among DBPs through computational and statistical analysis

32201/Next&Bio Inc., by the Strategies for Establishing Adverse outcome pathways (AOPs)
Fig. 1.
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