Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach
Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accuratel...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S016041202400182X |
| _version_ | 1797246871989649408 |
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| author | Miao Guan Xiaoyang Wang Xinyuan Xu Tianqi Ling Jing Wu Jinjun Qian Fei Ma Xiaowei Zhang |
| author_facet | Miao Guan Xiaoyang Wang Xinyuan Xu Tianqi Ling Jing Wu Jinjun Qian Fei Ma Xiaowei Zhang |
| author_sort | Miao Guan |
| collection | DOAJ |
| description | Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 μM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development. |
| first_indexed | 2024-04-24T19:49:42Z |
| format | Article |
| id | doaj.art-920cc26e71da4291b6e8ae21e479d2c7 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-24T19:49:42Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-920cc26e71da4291b6e8ae21e479d2c72024-03-25T04:17:07ZengElsevierEnvironment International0160-41202024-04-01186108596Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approachMiao Guan0Xiaoyang Wang1Xinyuan Xu2Tianqi Ling3Jing Wu4Jinjun Qian5Fei Ma6Xiaowei Zhang7Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd., Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd., Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd., Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd., Nanjing, Jiangsu 210023, ChinaDepartment of Psychology, College of Victoria College, University of Toronto, Toronto, ON, CA M5R 0A3, CanadaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Ave., Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd., Nanjing, Jiangsu 210023, China; Corresponding author.State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University, 163 Xianlin Ave., Nanjing, Jiangsu 210023, ChinaOrganophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 μM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development.http://www.sciencedirect.com/science/article/pii/S016041202400182XOrganophosphate flame retardants (OPFRs)Point of departure (POD)Molecular initiating event (MIE)Dose-dependent functional genomicsLipid metabolismERG2 (YMR202W) |
| spellingShingle | Miao Guan Xiaoyang Wang Xinyuan Xu Tianqi Ling Jing Wu Jinjun Qian Fei Ma Xiaowei Zhang Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach Environment International Organophosphate flame retardants (OPFRs) Point of departure (POD) Molecular initiating event (MIE) Dose-dependent functional genomics Lipid metabolism ERG2 (YMR202W) |
| title | Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach |
| title_full | Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach |
| title_fullStr | Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach |
| title_full_unstemmed | Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach |
| title_short | Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach |
| title_sort | bioactivity assessment of organophosphate flame retardants via a dose dependent yeast functional genomics approach |
| topic | Organophosphate flame retardants (OPFRs) Point of departure (POD) Molecular initiating event (MIE) Dose-dependent functional genomics Lipid metabolism ERG2 (YMR202W) |
| url | http://www.sciencedirect.com/science/article/pii/S016041202400182X |
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