Organophosphorus Flame Retardant TCPP Induces Cellular Senescence in Normal Human Skin Keratinocytes: Implication for Skin Aging

Tris (1-chloro-2-propyl) phosphate (TCPP) is one of the most frequently detected organophosphorus flames in the environment. Continuous daily exposure to TCPP may harm human skin. However, little is known about the adverse effects of TCPP on human skin. In this study, we first evaluated the detrimental effects and tried to uncover the underlying mechanisms of TCPP on human skin keratinocytes (HaCaT) after 24 h exposure. We found that TCPP caused a concentration-dependent decrease in HaCaT cell viability after exposure to 1.56-400 mu g/mL for 24 h, with an IC50 of 275 mu g/mL. TCPP also promoted the generation of intracellular reactive oxygen species (ROS) and triggered DNA damage, evidenced by an increase of phosphorylated histone H2A.X (gamma H2A.X) in the nucleus. Furthermore, the cell cycle was arrested at the G1 phase at 100 mu g/mL by upregulation of the mRNA expression of p53 and p21 and downregulation of cyclin D1 and CDK4 expression. Additionally, both the senescence-associated-beta-galactosidase activity and related proinflammatory cytokine IL-1 beta and IL-6 were elevated, indicating that TCPP exposure caused cellular senescence may be through the p53-dependent DNA damage signal pathway in HaCaT cells. Taken together, our data suggest that flame-retardant exposure may be a key precipitating factor for human skin aging.

Automated summary

Tris (1-chloro-2-propyl) phosphate (TCPP) is a commonly detected organophosphorus flame retardant in the environment. This study investigated the detrimental effects of TCPP on human skin keratinocytes and found that it decreased cell viability, induced reactive oxygen species generation and DNA damage, arrested the cell cycle at the G1 phase, and caused cellular senescence through the p53-dependent DNA damage signal pathway.