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 (LC50). 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.

中文翻译：

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正常人皮肤角质形成细胞中有机磷阻燃剂TDCPP诱导的细胞毒性及相关机制。

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，在包括室内灰尘在内的环境中经常被检测到。长期暴露于含有TDCPP的粉尘可能会对人体皮肤产生不利影响，但对其潜在的细胞毒性知之甚少。在这项研究中，人类皮肤角质形成细胞（HaCaT）被用于研究TDCPP诱导的细胞毒性及相关机制。研究了TDCPP对细胞形态，活力，凋亡和周期以及凋亡的mRNA水平（Bcl-2，Bax和Caspase-3）和细胞周期（cyclin D1，CDK2，CDK4和CDK6）调控基因的影响。结果表明，TDCPP暴露于TDCPP≥100μg/ mL 48小时后，引起细胞活力的浓度依赖性降低，中位致死浓度为163μg/ mL（LC50）。此外，除了抑制细胞周期蛋白D1，CDK2，CDK6和Bcl-2的表达外，TDCPP还可以通过增强Bax和Caspase-3的表达来诱导G0 / G1期细胞凋亡并以16和160μg/ mL的速率阻滞在G0 / G1期。我们的结果表明，TDCPP诱导的HaCaT细胞毒性可能是通过细胞凋亡和细胞周期停滞。这项研究提供了有关TDCPP对人皮肤细胞毒性的信息，这可能有助于减少TDCPP对人皮肤的毒性。