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三(2-氯乙基)磷酸酯(TDCPP)诱导正常人体皮肤角质形成细胞毒性及相关机制。

Organophosphorus flame retardant TDCPP-induced cytotoxicity and associated mechanisms in normal human skin keratinocytes.

机构信息

Yunnan Key Laboratory of Ecological Environment Evolution and Pollution Control in Mountainous Rural Areas, Institute of Environmental Remediation and Human Health, Southwest Forestry University, Kunming 650224, China.

Yunnan Key Laboratory of Ecological Environment Evolution and Pollution Control in Mountainous Rural Areas, Institute of Environmental Remediation and Human Health, Southwest Forestry University, Kunming 650224, China.

出版信息

Sci Total Environ. 2020 Jul 15;726:138526. doi: 10.1016/j.scitotenv.2020.138526. Epub 2020 Apr 8.

Abstract

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphorus flame retardant, has been frequently detected in the environment including indoor dust. Long-term exposure to TDCPP-containing dust may adversely affect human skin, however, little is known about its potential cytotoxicity. In this study, human skin keratinocytes (HaCaT) were employed to study TDCPP-induced cytotoxicity and associated mechanisms. The effects of TDCPP on cell morphology, viability, apoptosis, and cycle, and the mRNA levels of apoptosis (Bcl-2, Bax and Caspase-3) and cell cycle (cyclin D1, CDK2, CDK4 and CDK6) regulatory genes were investigated. The results showed that TDCPP caused a concentration-dependent decrease in cell viability after exposing to TDCPP ≥100 μg/mL for 48 h, with a median lethal concentration of 163 μg/mL (LC). In addition, TDCPP induced cell apoptosis and arrested cell cycle in the G0/G1 phase at 16 and 160 μg/mL by enhancing Bax and Caspase-3 expression besides inhibiting cyclin D1, CDK2, CDK6 and Bcl-2 expression. Our results showed that TDCPP-induced toxicity in HaCaT cells was probably through cell apoptosis and cell cycle arrest. This study provides information on the toxicity of TDCPP to human skin cells, which may help to reduce its toxicity to human skin.

摘要

磷酸三(1,3-二氯-2-丙基)酯(TDCPP)是一种广泛使用的有机磷阻燃剂,已在环境中包括室内灰尘中频繁检出。长期接触含 TDCPP 的灰尘可能会对人体皮肤造成不良影响,但是,其潜在的细胞毒性知之甚少。在这项研究中,用人皮肤角质形成细胞(HaCaT)来研究 TDCPP 诱导的细胞毒性及其相关机制。研究了 TDCPP 对细胞形态、活力、凋亡和细胞周期的影响,以及凋亡(Bcl-2、Bax 和 Caspase-3)和细胞周期(cyclin D1、CDK2、CDK4 和 CDK6)调节基因的 mRNA 水平。结果表明,在暴露于 TDCPP≥100μg/mL 48 h 后,TDCPP 导致细胞活力呈浓度依赖性下降,半数致死浓度(LC)为 163μg/mL。此外,TDCPP 通过增强 Bax 和 Caspase-3 的表达,同时抑制 cyclin D1、CDK2、CDK6 和 Bcl-2 的表达,在 16 和 160μg/mL 时诱导细胞凋亡并将细胞周期阻滞在 G0/G1 期。我们的结果表明,TDCPP 诱导 HaCaT 细胞毒性可能是通过细胞凋亡和细胞周期阻滞。本研究提供了 TDCPP 对人皮肤细胞毒性的信息,这可能有助于降低其对人皮肤的毒性。

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