Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages

摘要

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) is the most widely used organophosphorus flame retardant, which is now used instead of polybrominated diphenyl ethers (PBDEs). TDCPP has frequently been detected in inorganic environmental matrices, such as soil, water and air as well as biota. In vitro effects of TDCPP on cells had not been previously elucidated. Therefore, in the present study, cytotoxicity, DNA damage, cell cycle distribution, apoptosis caused by TDCPP was studied in RAW264.7 macrophage cells. TDCPP reduced viability of RAW264.7 cells in a concentration-dependent manner and caused damage to DNA that was detected by use of the comet assay and caused up-regulation of the level of γ-H2AX. TDCPP increased the intracellular reactive oxygen species (ROS) level in RAW264.7 cells up to 1.44-fold compared to the control group at 12 hr. Percentages of cells in G1 and G2 phases of the cell cycle were dose-dependently greater in cells exposed to TDCPP. TDCPP significantly down-regulated expression of CDK-4, Cyclin D1, Cyclin B1, CDC-2, which are regulators of G1 and G2 phases of the cell cycle. These results demonstrated that TDCPP is cytotoxic and damages DNA in RAW264.7 cells, which resulted in arrest of the cell cycle at G1 and G2 phases and resulted in apoptosis, suggest the necessity to evaluate the effects of TDCPP on the immune system at the cellular level.