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Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells
Yuan, Shengwu; Han, Yingnan; Ma, Mei; Rao, Kaifeng; Wang, Zijian; Yang, Rong; Liu, Yihong; Zhou, Xiaohong
2019-07
Source PublicationENVIRONMENTAL POLLUTION
ISSN0269-7491
Volume250Pages:58-67
AbstractAryl phosphorus-containing flame retardants (aryl-PFRs) have been frequently detected with increasingly used worldwide as one of alternatives for brominated flame retardants. However, information on their adverse effects on human health and ecosystem is insufficient, with limited study on their molecular mode of action in vitro. In this study, the cytotoxicity, DNA damage, mitochondrial impairment and the involved molecular mechanisms of certain frequently detectable aryl-PFRs, including 2-ethylhexyldiphenyl phosphate (EHDPP), methyl diphenyl phosphate (MDPP), bisphenol-A bis (diphenyl phosphate) (BDP), isodecyl diphenyl phosphate (IDPP), cresyl diphenyl phosphate (CDP) and the structurally similar and widely used organophosphorus pesticide chlorpyrifos (CPF), were evaluated in A549 cells using high-content screening (HCS) system. Aryl-PFRs showed different lethal concentration 50 (LC50) values ranging from 97.94 to 546.85 mu M in A549 cells using CCK-8 assay. EHDPP, IDPP, CDP, MDPP and CPF demonstrated an ability to induce DNA damage, evidenced by increased DNA content and S phase-reducing cell cycle arrest effect using fluorophore dye cocktail assay. Additionally, the selected aryl-PFRs induced mitochondrial impairment by the increasing mitochondrial mass and decreasing mitochondrial membrane potential. Moreover, BDP, MDPP, and CDP, which contain short alkyl chains showed their potential oxidative stress with intracellular ROS and mitochondrial superoxide over-production from an initially relatively low concentration. Additionally, based on the promotion of firefly luminescence in p53-transfected A549 cells, p53 activation was found to be involved in aryl-PFRs-induced DNA damage. Further real-time PCR results showed that all selected aryl-PFRs triggered p53/ p21/gadd45 beta-, and p53/p21/mdm2-mediated cell cycle pathways, and the p53/bax mediated apoptosis pathway to induce DNA damage and cytotoxic effects. These results suggest that aryl-PFRs (e.g., BDP, MDPP, CDP) cause oxidative stress-mediated DNA damage and mitochondrial impairment, and p53-dependent pathway was involved in the aryl-PFRs-induced DNA damage and cell cycle arrest. In conclusion, this study improves the understanding of PFRs-induced adverse outcomes and the involved molecular mechanism. (C) 2019 Elsevier Ltd. All rights reserved.
Department环境水质学国家重点实验室
KeywordPhosphorus-containing flame retardants Reactive oxygen species Mitochondrial damage p53 transfection Gene expression
Document Type期刊论文
Identifierhttp://ir.rcees.ac.cn/handle/311016/43062
Collection环境水质学国家重点实验室
Affiliation1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Key Lab Drinking Water Sci & Technol, Beijing 100085, Peoples R China
2.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Aquat Chem, Beijing 100085, Peoples R China
4.Beijing Water Qual Monitoring Ctr South To North, Beijing 100093, Peoples R China
5.Tsinghua Univ, Sch Environm, Ctr Sensor Technol Environm & Hlth, State Key Joint Lab,ESPC, Beijing 100084, Peoples R China
Recommended Citation
GB/T 7714
Yuan, Shengwu,Han, Yingnan,Ma, Mei,et al. Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells[J]. ENVIRONMENTAL POLLUTION,2019,250:58-67.
APA Yuan, Shengwu.,Han, Yingnan.,Ma, Mei.,Rao, Kaifeng.,Wang, Zijian.,...&Zhou, Xiaohong.(2019).Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells.ENVIRONMENTAL POLLUTION,250,58-67.
MLA Yuan, Shengwu,et al."Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells".ENVIRONMENTAL POLLUTION 250(2019):58-67.
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