Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway?
Organophosphorus flame retardants (OPFRs) have been frequently detected with relatively high concentrations in various environmental media and are considered emerging environmental pollutants. However, their biological effect and underlying mechanism is still unclear, and whether chlorinated OPFRs (...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324002331 |
| _version_ | 1797261880728748032 |
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| author | Shengwu Yuan Hong Zhang Shuhang Wang Xia Jiang Mei Ma Yiping Xu Yingnan Han Zijian Wang |
| author_facet | Shengwu Yuan Hong Zhang Shuhang Wang Xia Jiang Mei Ma Yiping Xu Yingnan Han Zijian Wang |
| author_sort | Shengwu Yuan |
| collection | DOAJ |
| description | Organophosphorus flame retardants (OPFRs) have been frequently detected with relatively high concentrations in various environmental media and are considered emerging environmental pollutants. However, their biological effect and underlying mechanism is still unclear, and whether chlorinated OPFRs (Cl-OPFRs) cause adverse outcomes with the same molecular initial events or share the same key events (KEs) remains unknown. In this study, in vitro bioassays were conducted to analyze the cytotoxicity, mitochondrial impairment, DNA damage and molecular mechanisms of two Cl-OPFRs. The results showed that these two Cl-OPFRs, which have similar structures, induced severe cellular and molecular damages via different underlying mechanisms. Both tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) (TCPP) induced oxidative stress-mediated mitochondrial impairment and DNA damage, as shown by the overproduction of intracellular reactive oxygen species (ROS) and mitochondrial superoxide. Furthermore, the DNA damage caused by TCPP resulted in p53/p21-mediated cell cycle arrest, as evidenced by flow cytometry and real-time PCR. At the cellular and molecular levels, TCPP increased the sub-G1 apoptotic peak and upregulated the p53/Bax apoptosis pathway, possibly resulted in apoptosis associated with its stronger cytotoxicity. Although structurally similar to TCPP, TCEP did not induce mitochondrial impairment and DNA damage by the same KEs. These results provide insight into the toxicity of Cl-OPFRs with similar structures but different mechanisms, which is of great significance for constructing adverse outcome pathways or determining intermediate KEs. |
| first_indexed | 2024-03-07T20:06:34Z |
| format | Article |
| id | doaj.art-f836ee0218da4d3ba926594174e9dee4 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-24T23:48:15Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-f836ee0218da4d3ba926594174e9dee42024-03-15T04:42:54ZengElsevierEcotoxicology and Environmental Safety0147-65132024-03-01273116158Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway?Shengwu Yuan0Hong Zhang1Shuhang Wang2Xia Jiang3Mei Ma4Yiping Xu5Yingnan Han6Zijian Wang7State Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environment Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Science, Beijing 100012, ChinaState Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environment Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Science, Beijing 100012, ChinaState Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environment Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Science, Beijing 100012, China; Corresponding author.State Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environment Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Science, Beijing 100012, ChinaKey Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author at: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, ChinaKey Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, ChinaKey Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, ChinaOrganophosphorus flame retardants (OPFRs) have been frequently detected with relatively high concentrations in various environmental media and are considered emerging environmental pollutants. However, their biological effect and underlying mechanism is still unclear, and whether chlorinated OPFRs (Cl-OPFRs) cause adverse outcomes with the same molecular initial events or share the same key events (KEs) remains unknown. In this study, in vitro bioassays were conducted to analyze the cytotoxicity, mitochondrial impairment, DNA damage and molecular mechanisms of two Cl-OPFRs. The results showed that these two Cl-OPFRs, which have similar structures, induced severe cellular and molecular damages via different underlying mechanisms. Both tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) (TCPP) induced oxidative stress-mediated mitochondrial impairment and DNA damage, as shown by the overproduction of intracellular reactive oxygen species (ROS) and mitochondrial superoxide. Furthermore, the DNA damage caused by TCPP resulted in p53/p21-mediated cell cycle arrest, as evidenced by flow cytometry and real-time PCR. At the cellular and molecular levels, TCPP increased the sub-G1 apoptotic peak and upregulated the p53/Bax apoptosis pathway, possibly resulted in apoptosis associated with its stronger cytotoxicity. Although structurally similar to TCPP, TCEP did not induce mitochondrial impairment and DNA damage by the same KEs. These results provide insight into the toxicity of Cl-OPFRs with similar structures but different mechanisms, which is of great significance for constructing adverse outcome pathways or determining intermediate KEs.http://www.sciencedirect.com/science/article/pii/S0147651324002331Chlorinated organophosphorus flame retardantsToxicityDNA damageMolecular mechanism |
| spellingShingle | Shengwu Yuan Hong Zhang Shuhang Wang Xia Jiang Mei Ma Yiping Xu Yingnan Han Zijian Wang Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway? Ecotoxicology and Environmental Safety Chlorinated organophosphorus flame retardants Toxicity DNA damage Molecular mechanism |
| title | Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway? |
| title_full | Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway? |
| title_fullStr | Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway? |
| title_full_unstemmed | Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway? |
| title_short | Do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and DNA damage share the same pathway? |
| title_sort | do the same chlorinated organophosphorus flame retardants that cause cytotoxicity and dna damage share the same pathway |
| topic | Chlorinated organophosphorus flame retardants Toxicity DNA damage Molecular mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324002331 |
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