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In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals
Since initial regulatory action in 2010 in Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potent...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936204/ https://www.ncbi.nlm.nih.gov/pubmed/36534918 http://dx.doi.org/10.1093/toxsci/kfac127 |
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author | Matteo, Geronimo Leingartner, Karen Rowan-Carroll, Andrea Meier, Matthew Williams, Andrew Beal, Marc A Gagné, Matthew Farmahin, Reza Wickramasuriya, Shamika Reardon, Anthony J F Barton-Maclaren, Tara Christopher Corton, J Yauk, Carole L Atlas, Ella |
author_facet | Matteo, Geronimo Leingartner, Karen Rowan-Carroll, Andrea Meier, Matthew Williams, Andrew Beal, Marc A Gagné, Matthew Farmahin, Reza Wickramasuriya, Shamika Reardon, Anthony J F Barton-Maclaren, Tara Christopher Corton, J Yauk, Carole L Atlas, Ella |
author_sort | Matteo, Geronimo |
collection | PubMed |
description | Since initial regulatory action in 2010 in Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potential hazards and compare potencies of BPA and 15 BPA alternative chemicals in cultured breast cancer cells. MCF-7 cells were exposed to BPA and 15 alternative chemicals (0.0005–100 µM) for 48 h. TempO-Seq (BioSpyder Inc) was used to examine global transcriptomic changes and estrogen receptor alpha (ERα)-associated transcriptional changes. Benchmark concentration (BMC) analysis was conducted to identify 2 global transcriptomic points of departure: (1) the lowest pathway median gene BMC and (2) the 25th lowest rank-ordered gene BMC. ERα activation was evaluated using a published transcriptomic biomarker and an ERα-specific transcriptomic point of departure was derived. Genes fitting BMC models were subjected to upstream regulator and canonical pathway analysis in Ingenuity Pathway Analysis. Biomarker analysis identified BPA and 8 alternative chemicals as ERα active. Global and ERα transcriptomic points of departure produced highly similar potency rankings with bisphenol AF as the most potent chemical tested, followed by BPA and bisphenol C. Further, BPA and transcriptionally active alternative chemicals enriched similar gene sets associated with increased cell division and cancer-related processes. These data provide support for future read-across applications of transcriptomic profiling for risk assessment of data-poor chemicals and suggest that several BPA alternative chemicals may cause hazards at similar concentrations to BPA. |
format | Online Article Text |
id | pubmed-9936204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99362042023-02-18 In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals Matteo, Geronimo Leingartner, Karen Rowan-Carroll, Andrea Meier, Matthew Williams, Andrew Beal, Marc A Gagné, Matthew Farmahin, Reza Wickramasuriya, Shamika Reardon, Anthony J F Barton-Maclaren, Tara Christopher Corton, J Yauk, Carole L Atlas, Ella Toxicol Sci Endocrine Toxicology Since initial regulatory action in 2010 in Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potential hazards and compare potencies of BPA and 15 BPA alternative chemicals in cultured breast cancer cells. MCF-7 cells were exposed to BPA and 15 alternative chemicals (0.0005–100 µM) for 48 h. TempO-Seq (BioSpyder Inc) was used to examine global transcriptomic changes and estrogen receptor alpha (ERα)-associated transcriptional changes. Benchmark concentration (BMC) analysis was conducted to identify 2 global transcriptomic points of departure: (1) the lowest pathway median gene BMC and (2) the 25th lowest rank-ordered gene BMC. ERα activation was evaluated using a published transcriptomic biomarker and an ERα-specific transcriptomic point of departure was derived. Genes fitting BMC models were subjected to upstream regulator and canonical pathway analysis in Ingenuity Pathway Analysis. Biomarker analysis identified BPA and 8 alternative chemicals as ERα active. Global and ERα transcriptomic points of departure produced highly similar potency rankings with bisphenol AF as the most potent chemical tested, followed by BPA and bisphenol C. Further, BPA and transcriptionally active alternative chemicals enriched similar gene sets associated with increased cell division and cancer-related processes. These data provide support for future read-across applications of transcriptomic profiling for risk assessment of data-poor chemicals and suggest that several BPA alternative chemicals may cause hazards at similar concentrations to BPA. Oxford University Press 2022-12-19 /pmc/articles/PMC9936204/ /pubmed/36534918 http://dx.doi.org/10.1093/toxsci/kfac127 Text en © His Majesty the King in Right of Canada, as represented by the Minister of Health, 2022. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Endocrine Toxicology Matteo, Geronimo Leingartner, Karen Rowan-Carroll, Andrea Meier, Matthew Williams, Andrew Beal, Marc A Gagné, Matthew Farmahin, Reza Wickramasuriya, Shamika Reardon, Anthony J F Barton-Maclaren, Tara Christopher Corton, J Yauk, Carole L Atlas, Ella In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals |
title |
In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals |
title_full |
In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals |
title_fullStr |
In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals |
title_full_unstemmed |
In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals |
title_short |
In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals |
title_sort | in vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor bpa alternative chemicals |
topic | Endocrine Toxicology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936204/ https://www.ncbi.nlm.nih.gov/pubmed/36534918 http://dx.doi.org/10.1093/toxsci/kfac127 |
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