A Tiered Approach for Screening and Assessment of Environmental Mixtures by Omics and In Vitro Assays
New methodology approaches with a broad coverage of the biological effects are urgently needed to evaluate the safety of the universe of environmentally relevant chemicals. Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The m...
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| Veröffentlicht in: | Environmental science & technology 2020-06, Vol.54 (12), p.7430-7439 |
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| creator | Fang, Wendi Peng, Ying Yan, Lu Xia, Pu Zhang, Xiaowei |
| description | New methodology approaches with a broad coverage of the biological effects are urgently needed to evaluate the safety of the universe of environmentally relevant chemicals. Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The mixture samples and the perturbated biological pathways are prioritized by concentration-dependent transcriptome (CDT), and then be used to guide the selection of in vitro bioassays for toxicant identification. To evaluate omics' screening capability, we first applied a CDT technique to test mixture samples by HepG2 and MCF7 cells. Effect recoveries of large-volume solid-phase extraction on overall bioactivity of mixture were 48.9% in HepG2 and 58.3% in MCF7. The overall bioactivity potencies obtained by transcriptomics were positively correlated with the panel of 8 bioassays among 14 mixture samples combining with the previous data. Transcriptomics could predict their activation status (AUC=0.783) and relative potency (p |
| doi_str_mv | 10.1021/acs.est.0c00662 |
| format | Article |
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Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The mixture samples and the perturbated biological pathways are prioritized by concentration-dependent transcriptome (CDT), and then be used to guide the selection of in vitro bioassays for toxicant identification. To evaluate omics' screening capability, we first applied a CDT technique to test mixture samples by HepG2 and MCF7 cells. Effect recoveries of large-volume solid-phase extraction on overall bioactivity of mixture were 48.9% in HepG2 and 58.3% in MCF7. The overall bioactivity potencies obtained by transcriptomics were positively correlated with the panel of 8 bioassays among 14 mixture samples combining with the previous data. Transcriptomics could predict their activation status (AUC=0.783) and relative potency (p<0.05) of bioassays for 4 of the 8 receptors (AhR, ER, AR and Nrf2). Furthermore, the CDT identified other biological pathways perturbated by mixture samples, such as the pathway related to TP53, CAR, FXR, HIF, THRA et al. 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Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The mixture samples and the perturbated biological pathways are prioritized by concentration-dependent transcriptome (CDT), and then be used to guide the selection of in vitro bioassays for toxicant identification. To evaluate omics' screening capability, we first applied a CDT technique to test mixture samples by HepG2 and MCF7 cells. Effect recoveries of large-volume solid-phase extraction on overall bioactivity of mixture were 48.9% in HepG2 and 58.3% in MCF7. The overall bioactivity potencies obtained by transcriptomics were positively correlated with the panel of 8 bioassays among 14 mixture samples combining with the previous data. Transcriptomics could predict their activation status (AUC=0.783) and relative potency (p<0.05) of bioassays for 4 of the 8 receptors (AhR, ER, AR and Nrf2). Furthermore, the CDT identified other biological pathways perturbated by mixture samples, such as the pathway related to TP53, CAR, FXR, HIF, THRA et al. 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| subjects | Bioassays Biological activity Biological effects Environmental assessment Evaluation Gene expression In vitro methods and tests p53 Protein Quality assessment Quality control Screening Solid phases Toxicants Water quality Water quality assessments |
| title | A Tiered Approach for Screening and Assessment of Environmental Mixtures by Omics and In Vitro Assays |
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