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三(1,3-二氯-2-丙基)磷酸酯诱导的人 A549 细胞毒性及其相关机制。

Tris(1,3-dichloro-2-propyl) phosphate-induced cytotoxicity and its associated mechanisms in human A549 cells.

机构信息

Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Control and Prevention, Beijing, China.

出版信息

Toxicol Ind Health. 2024 Jul;40(7):387-397. doi: 10.1177/07482337241255711. Epub 2024 May 10.

Abstract

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardant and has been detected in various environmental matrices including indoor dust. Inhalation of indoor dust is one of the most important pathways for human exposure to TDCIPP. However, its adverse effects on human lung cells and potential impacts on respiratory toxicity are largely unknown. In the current study, human non-small cell carcinoma (A549) cells were selected as a cell model, and the effects of TDCIPP on cell viability, cell cycle, cell apoptosis, and underlying molecular mechanisms were investigated. Our data indicated a concentration-dependent decrease in the cell viability of A549 cells after exposure to TDCIPP for 48 h, with half lethal concentration (LC) being 82.6 µM. In addition, TDCIPP caused cell cycle arrest mainly in the G0/G1 phase by down-regulating the mRNA expression of , and , while up-regulating the mRNA expression of and . In addition, cell apoptosis was induced via altering the expression levels of , , and . Our study implies that TDCIPP may pose potential health risks to the human respiratory system and its toxicity should not be neglected.

摘要

磷酸三(1,3-二氯丙基)酯(TDCIPP)是一种广泛使用的有机磷阻燃剂,已在包括室内灰尘在内的各种环境基质中检测到。吸入室内灰尘是人类接触 TDCIPP 的最重要途径之一。然而,其对人体肺细胞的不良影响及其对呼吸毒性的潜在影响在很大程度上尚不清楚。在当前的研究中,选择人非小细胞肺癌(A549)细胞作为细胞模型,研究了 TDCIPP 对细胞活力、细胞周期、细胞凋亡以及潜在分子机制的影响。我们的数据表明,A549 细胞在接触 TDCIPP 48 小时后,细胞活力呈浓度依赖性下降,半数致死浓度(LC)为 82.6 μM。此外,TDCIPP 通过下调 、 和 的 mRNA 表达,同时上调 的 mRNA 表达,导致细胞周期主要停滞在 G0/G1 期。此外,通过改变 的表达水平诱导细胞凋亡 、 和 。我们的研究表明,TDCIPP 可能对人体呼吸系统造成潜在的健康风险,其毒性不应被忽视。

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