Different responses of zebrafish and human-based estrogenicity bioassays to selected environmental contaminants and their mixtures

Abstract : Effect-based tools (EBT) based on estrogen receptor (ER) activation are widely used to monitor xeno-estrogens in environmental samples. We previously reported that established human (MELN cells, expressing hERα) and zebrafish (ZELHα cells expressing zfERα, ZELHβ2 cells expressing zfERβ2) reporter cell lines are robust, reliable and sensitive to detect well-known ER ligands. However, they can respond to surface water and effluents samples differently, with samples being selectively active either on human or zebrafish cells. Different responses may be due to non-identified active substances and/or interactions with other chemicals, as ER activation depends on the intrinsic potency of the chemical and on the cell context (e.g. metabolism). Therefore, the present study aimed to compare the responses of zebrafish and human EBT to selected environmental pollutants, alone and in combination. Interactions between chemicals were taken into account by (1) assessing both activation and inhibition of ER response, (2) using concentration addition (CA) model to predict additive effects, and (3) combining active and non-active pollutants. While genistein and bisphenol A (BPA) were active on all EBTs, marked differences were observed for other chemicals. Triphenylphosphate (TPP) and benzo(a)pyrene (BaP) induced ER activation in MELN cells but decreased E2 response in zebrafish cells. Chlorophene, benzo(b)fluoranthene and propiconazole selectively inhibited the E2-induced reporter gene response in zebrafish cells. The first 12-component mixture results indicated that the effects in ZELHα and ZELHβ2 cells were driven by inhibiting chemicals (TPP and propiconazole), while the estrogenic activity of BPA and genistein was not detected, although predicted. In MELN cells, the estrogenic response (driven by genistein, BPA and TPP) agreed overall well with CA prediction. Work is ongoing with other mixture designs. Altogether, the results indicate that both the cell context (fish vs human) and the effects of anti-estrogenic chemicals influence ER response. In line with previous observations on environmental samples, our study raises the question of cross-species differences and fish-specific effects, highlighting the importance of the cell model for water quality biomonitoring. Future work will focus on the refinement of estrogenicity assessment by taking into account anti-estrogenic effects in environmental samples. This work was performed within the EU FP7 project SOLUTIONS.
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Hélène Serra, François Brion, M. Scholze, W. Busch, Rolf Altenburger, et al.. Different responses of zebrafish and human-based estrogenicity bioassays to selected environmental contaminants and their mixtures. 27. SETAC Europe annual meeting, May 2017, Bruxelles, France. ⟨ineris-01863855⟩

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