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

摘要

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, Box 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_(50)). In addition, TDCPP induced cell apoptosis and arrested cell cycle in the G0/G1 phase at 16 and 160 μg/mL by enhancing Box and Caspase-3 expression besides inhibiting cydin 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.