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Combined effects of environmental xeno-estrogens within multi-component mixtures : Comparison of in vitro human- and zebrafish-based estrogenicity bioassays

Serra, Hélène LU ; Scholze, Martin ; Altenburger, Rolf ; Busch, Wibke ; Budzinski, Hélène ; Brion, François and Aït-aïssa, Selim (2019) In Chemosphere 227. p.334-344
Abstract
Some recent studies showed that in vitro bioassays based on fish or human estrogen receptor (ER) activation may have distinct responses to environmental samples, highlighting the need to better understand bioassay-specific ER response to environmental mixtures. For this purpose, we investigated a 12-compound mixture in two mixture ratios (M1 and M2) on zebrafish (zf) liver cells stably expressing zfERα (ZELHα cells) or zfERβ2 (ZELHβ2 cells) and on human ER-reporter gene (MELN) cells. The mixture included the well-known ER ligands bisphenol A (BPA) and genistein (GEN), and other compounds representatives of a freshwater background contamination. In this context, the study aimed at assessing the robustness of concentration addition (CA)... (More)
Some recent studies showed that in vitro bioassays based on fish or human estrogen receptor (ER) activation may have distinct responses to environmental samples, highlighting the need to better understand bioassay-specific ER response to environmental mixtures. For this purpose, we investigated a 12-compound mixture in two mixture ratios (M1 and M2) on zebrafish (zf) liver cells stably expressing zfERα (ZELHα cells) or zfERβ2 (ZELHβ2 cells) and on human ER-reporter gene (MELN) cells. The mixture included the well-known ER ligands bisphenol A (BPA) and genistein (GEN), and other compounds representatives of a freshwater background contamination. In this context, the study aimed at assessing the robustness of concentration addition (CA) model and the potential confounding influence of other chemicals by testing subgroups of ER activators, ER inhibitors or ER activators and inhibitors combined. Individual chemical testing showed a higher prevalence of ER inhibitors in zebrafish than human cells (e.g. propiconazole), and some chemicals inhibited zfER but activated hER response (e.g. benzo(a)pyrene, triphenylphosphate). The estrogenic activity of M1 and M2 was well predicted by CA in MELN cells, whereas it was significantly lower than predicted in ZELHβ2 cells, contrasting with the additive effects observed for BPA and GEN binary mixtures. When testing the subgroups of ER activators and inhibitors combined, the deviation from additivity in ZELHβ2 cells was caused by zebrafish-specific inhibiting chemicals. This study provides novel information on the ability of environmental pollutants to interfere with zfER signalling and shows that non-estrogenic chemicals can influence the response to a mixture of xeno-estrogens in a bioassay-specific manner. (Less)
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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Chemosphere
volume
227
pages
334 - 344
publisher
Elsevier
external identifiers
  • scopus:85064507098
  • pmid:30999174
ISSN
0045-6535
DOI
10.1016/j.chemosphere.2019.04.060
language
English
LU publication?
no
id
a0767d8d-2a9d-4142-a4ea-b5930f1b7bc0
date added to LUP
2019-04-18 14:48:46
date last changed
2022-04-25 22:30:06
@article{a0767d8d-2a9d-4142-a4ea-b5930f1b7bc0,
  abstract     = {{Some recent studies showed that in vitro bioassays based on fish or human estrogen receptor (ER) activation may have distinct responses to environmental samples, highlighting the need to better understand bioassay-specific ER response to environmental mixtures. For this purpose, we investigated a 12-compound mixture in two mixture ratios (M1 and M2) on zebrafish (zf) liver cells stably expressing zfERα (ZELHα cells) or zfERβ2 (ZELHβ2 cells) and on human ER-reporter gene (MELN) cells. The mixture included the well-known ER ligands bisphenol A (BPA) and genistein (GEN), and other compounds representatives of a freshwater background contamination. In this context, the study aimed at assessing the robustness of concentration addition (CA) model and the potential confounding influence of other chemicals by testing subgroups of ER activators, ER inhibitors or ER activators and inhibitors combined. Individual chemical testing showed a higher prevalence of ER inhibitors in zebrafish than human cells (e.g. propiconazole), and some chemicals inhibited zfER but activated hER response (e.g. benzo(a)pyrene, triphenylphosphate). The estrogenic activity of M1 and M2 was well predicted by CA in MELN cells, whereas it was significantly lower than predicted in ZELHβ2 cells, contrasting with the additive effects observed for BPA and GEN binary mixtures. When testing the subgroups of ER activators and inhibitors combined, the deviation from additivity in ZELHβ2 cells was caused by zebrafish-specific inhibiting chemicals. This study provides novel information on the ability of environmental pollutants to interfere with zfER signalling and shows that non-estrogenic chemicals can influence the response to a mixture of xeno-estrogens in a bioassay-specific manner.}},
  author       = {{Serra, Hélène and Scholze, Martin and Altenburger, Rolf and Busch, Wibke and Budzinski, Hélène and Brion, François and Aït-aïssa, Selim}},
  issn         = {{0045-6535}},
  language     = {{eng}},
  month        = {{07}},
  pages        = {{334--344}},
  publisher    = {{Elsevier}},
  series       = {{Chemosphere}},
  title        = {{Combined effects of environmental xeno-estrogens within multi-component mixtures : Comparison of in vitro human- and zebrafish-based estrogenicity bioassays}},
  url          = {{http://dx.doi.org/10.1016/j.chemosphere.2019.04.060}},
  doi          = {{10.1016/j.chemosphere.2019.04.060}},
  volume       = {{227}},
  year         = {{2019}},
}