Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Combination of metabolomics with cellular assays reveals new biomarkers and mechanistic insights on xenoestrogenic exposures in MCF-7 cells
Autor Potratz, S.; Tarnow, P.; Jungnickel, H.; Baumann, S.; von Bergen, M.; Tralau, T.; Luch, A.;
Journal / Serie Chemical Research in Toxicology
Erscheinungsjahr 2017
Department MOLSYB;
Band/Volume 30
Heft 4
Sprache englisch;
POF III (gesamt) F11;
UFZ Querschnittsthemen RU3;
Abstract The disruptive potential of xenoestrogens like bisphenol A (BPA) lies in their 17β-estradiol (E2)-like binding to estrogen receptors (ERs) followed by concomitant modulation of ER target gene expression. Unsurprisingly most endocrine testing systems focus on the quantification of canonical transcripts or ER-sensitive reporters. However, only little information is available about the corresponding metabolomic changes in vitro. This knowledge gap becomes particularly relevant in the context of potential mixture effects, for example as a consequence of co-exposure to potentially estrogenically active pollutants (e.g., Cd2+). Such effects are often difficult to dissect with molecular tools, especially with regard to potential physiological relevance. Metabolomic biomarkers are well-suited to address this latter aspect as they provide a comprehensive readout of whole-cell physiology. Applying a targeted metabolomics approach (FIA-MS/MS), this study looked for biomarkers indicative of xenoestrogenic exposure in MCF-7 cells. Cells were treated with E2 and BPA in the presence or absence of Cd2+. Statistical analysis revealed a total of 11 amino acids and phospholipids to be related to compound’s estrogenic potency. Co-exposure to Cd2+ modulated the estrogenic profile. However, the corresponding changes were found to be moderate with cellular assays such as the E-screen failing to record any Cd2+-specific estrogenic effects. Overall metabolomics analysis identified proline as the most prominent estrogenic biomarker. Its increase could clearly be related to estrogenic exposure and concomitant ERα-mediated induction of proliferation. Involvement of the latter was confirmed by siRNA-mediated knockdown studies as well as by receptor inhibition. Further, the underlying signaling was also found to involve the oncoprotein MYC. Taken together this study provides insights in the underlying mechanisms of xenoestrogenic effects and exemplify the strength of the complementary use of metabolomics and cellular and molecular assays.
ID 17772
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=17772
Potratz, S., Tarnow, P., Jungnickel, H., Baumann, S., von Bergen, M., Tralau, T., Luch, A. (2017):
Combination of metabolomics with cellular assays reveals new biomarkers and mechanistic insights on xenoestrogenic exposures in MCF-7 cells
Chem. Res. Toxicol. 30 (4), 883 - 892