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

IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Toxicology and Industrial Health Pub Date : 2024-07-01 Epub Date: 2024-05-10 DOI:10.1177/07482337241255711
Yixing Feng, Ming Li, Jie Yin, Jiachen Shi, Qian Jiang, Jing Zhang
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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 (LC50) being 82.6 µM. In addition, TDCIPP caused cell cycle arrest mainly in the G0/G1 phase by down-regulating the mRNA expression of cyclin D1, CDK4, and CDK6, while up-regulating the mRNA expression of p21 and p27. In addition, cell apoptosis was induced via altering the expression levels of Bcl-2, BAX, and BAK. Our study implies that TDCIPP may pose potential health risks to the human respiratory system and its toxicity should not be neglected.

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磷酸三(1,3-二氯-2-丙基)酯在人类 A549 细胞中诱导的细胞毒性及其相关机制。
磷酸三(1,3-二氯-2-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,它对人体肺部细胞的不良影响以及对呼吸系统毒性的潜在影响在很大程度上还不为人所知。本研究选择了人类非小细胞癌(A549)细胞作为细胞模型,研究了 TDCIPP 对细胞活力、细胞周期、细胞凋亡的影响及其潜在的分子机制。我们的数据表明,A549 细胞暴露于 TDCIPP 48 小时后,其细胞活力呈浓度依赖性下降,半致死浓度(LC50)为 82.6 µM。此外,TDCIPP 通过下调细胞周期蛋白 D1、CDK4 和 CDK6 的 mRNA 表达,同时上调 p21 和 p27 的 mRNA 表达,导致细胞周期主要停滞在 G0/G1 期。此外,细胞凋亡是通过改变 Bcl-2、BAX 和 BAK 的表达水平来诱导的。我们的研究表明,TDCIPP 可能会对人体呼吸系统造成潜在的健康风险,其毒性不容忽视。
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来源期刊
CiteScore
3.50
自引率
5.30%
发文量
72
审稿时长
4 months
期刊介绍: Toxicology & Industrial Health is a journal dedicated to reporting results of basic and applied toxicological research with direct application to industrial/occupational health. Such research includes the fields of genetic and cellular toxicology and risk assessment associated with hazardous wastes and groundwater.
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