Universität zu Köln

Lucendo-Villarin, B., Nell, P., Hellwig, B., Filis, P., Feuerborn, D., O'Shaughnessy, P. J., Godoy, P., Rahnenfuehrer, J., Hengstler, J. G., Cherianidou, A., Sachinidis, A., Fowler, P. A. and Hay, D. C. (2020). GENOME-WIDE EXPRESSION CHANGES INDUCED BY BISPHENOL A, F AND S IN HUMAN STEM CELL DERIVED HEPATOCYTE-LIKE CELLS. EXCLI J., 19. S. 1459 - 1477. DORTMUND: EXCLI JOURNAL MANAGING OFFICE. ISSN 1611-2156

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Abstract

The debate about possible adverse effects of bisphenol A (BPA) has been ongoing for decades. Bisphenol F (BPF) and S (BPS) have been suggested as safer alternatives. In the present study we used hepatocyte-like cells (HLCs) derived from the human embryonic stem cell lines Man12 and H9 to compare the three bisphenol derivatives. Stem cell-derived progenitors were produced using an established system and were exposed to BPA, BPF and BPS for 8 days during their transition to HLCs. Subsequently, we examined cell viability, inhibition of cytochrome P450 (CYP) activity, and genome-wide RNA profiles. Sub-cytotoxic, inhibitory concentrations (IC50) of CYP3A were 20, 9.5 and 25 mu M for BPA, BPF and BPS in Man12 derived HLCs, respectively. The corresponding concentrations for H9-derived HLCs were 19, 29 and 31 mu M. These IC50 concentrations were used to study global expression changes in this in vitro study and are higher than unconjugated BPA in serum of the general population. A large overlap of up- as well as downregulated genes induced by the three bisphenol derivatives was seen. This is at least 28-fold higher compared to randomly expected gene expression changes. Moreover, highly significant correlations of expression changes induced by the three bisphenol derivatives were obtained in pairwise comparisons. Dysregulated genes were associated with reduced metabolic function, cellular differentiation, embryonic development, cell survival and apoptosis. In conclusion, no major differences in cytochrome inhibitory activities of BPA, BPF and BPS were observed and gene expression changes showed a high degree of similarity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lucendo-Villarin, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nell, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellwig, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Filis, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Feuerborn, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Shaughnessy, P. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Godoy, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahnenfuehrer, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hengstler, J. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cherianidou, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fowler, P. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hay, D. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-349699
DOI:	10.17179/excli2020-2934
Journal or Publication Title:	EXCLI J.
Volume:	19
Page Range:	S. 1459 - 1477
Date:	2020
Publisher:	EXCLI JOURNAL MANAGING OFFICE
Place of Publication:	DORTMUND
ISSN:	1611-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA; WIDESPREAD EXPOSURE; P53; ACTIVATION; LIVER; DIFFERENTIATION; INJURY Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34969