有机磷阻燃剂对人肺癌A549细胞的毒性效应及机制

沈铖澄, 杨先海, 刘会会

中国环境科学 ›› 2025, Vol. 45 ›› Issue (6) : 3451-3459.

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中国环境科学 ›› 2025, Vol. 45 ›› Issue (6) : 3451-3459.
环境毒理与健康

有机磷阻燃剂对人肺癌A549细胞的毒性效应及机制

  • 沈铖澄, 杨先海, 刘会会
作者信息 +

Study on the toxic effect and mechanism of organophosphorus flame retardants on the human lung cancer A549cell

  • SHEN Cheng-cheng, YANG Xian-hai, LIU Hui-hui
Author information +
文章历史 +

摘要

以A549人肺癌细胞作为体外模型,选取环境中检出频率较高的3种有机磷阻燃剂:磷酸三(2-丁氧基)乙酯(TBOEP)、磷酸三(2-氯丙基)酯(TCIPP)和磷酸三异丙基苯酯(IPPP)作为代表性物质,通过多种毒性测试终点,研究它们对人肺癌A549细胞的毒性效应.结果表明,3种OPFRs均能抑制细胞活力、刺激其产生过量的活性氧、降低细胞内线粒体膜电位、诱导细胞产生炎症、引起DNA损伤.每个细胞毒性指标都呈现出剂量依赖性.低浓度的OPFRs影响较小,随着OPFRs浓度升高,毒性效应越来越大.对比3种OPFRs,A549细胞毒性作用顺序为TBOEP > TCIPP ≈ IPPP.特别是在高浓度500 μmol/L的TBOEP暴露下,细胞活力不到5%,细胞内活性氧水平上升3倍,线粒体膜电位降低了46.5%,炎症因子IL-6和TNF-α的分泌量上升了124.4%和262.7%,DNA损伤标记物含量显著增加.本文研究结果为揭示不同OPFRs的毒性差异提供了新的实验数据和思路,为评估环境中OPFRs对人体健康风险提供了新的见解.

Abstract

Human lung cancer cell A549were used as the test cell. Three kinds of organophosphorus flame retardants, i.e., tris(2-butoxyethyl) phosphate (TBOEP), tris(1-chloro-2-propyl)phosphate (TCIPP), and tri(4-isopropylphenyl)phosphate (IPPP), were selected as representative compounds, which are frequently detected in the environment. The toxic effects of the three compounds on A549cell were studied through multiple toxicity test endpoints. Results showed that the three OPFRs could inhibit cell viability, stimulate the production of excessive reactive oxygen species and reduce the mitochondrial membrane potential in cell, induce cell inflammation and cause DNA damage. All the cytotoxicity indicators were dose-dependent. OPFRs with low concentrations had less effect, and the toxic effect enhanced with the increase of OPFRs concentrations. Compared with the three OPFRs, their toxic effects on A549cells ranked as TBOEP > TCIPP ≈ IPPP. Especially, when the cells were exposed to TBOEP with a high concentration of 500 μmol/L, the cell viability was less than 5%, the amount of reactive oxygen species in cell increased by three times, the mitochondrial membrane potential decreased by 46.5%, the secretion of inflammatory factors IL-6 and TNF-α increased by 124.4% and 262.7%, and the content of DNA damage markers increased significantly.

关键词

DNA损伤 / 细胞毒性 / 线粒体损伤 / 氧化应激 / 有机磷阻燃剂

Key words

cytotoxicity / DNA damage / mitochondrial damage / organophosphate flame retardants / oxidative stress

引用本文

导出引用
沈铖澄, 杨先海, 刘会会. 有机磷阻燃剂对人肺癌A549细胞的毒性效应及机制[J]. 中国环境科学. 2025, 45(6): 3451-3459
SHEN Cheng-cheng, YANG Xian-hai, LIU Hui-hui. Study on the toxic effect and mechanism of organophosphorus flame retardants on the human lung cancer A549cell[J]. China Environmental Science. 2025, 45(6): 3451-3459
中图分类号: X503.1   

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基金

国家自然科学基金资助项目(22176097)

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